VCV000003558.2 - ClinVar

NM_001370497.1(ABCC11):c.538G>A (p.Gly180Arg)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Benign
Benign (1)

1 out of 4 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001370497.1(ABCC11):c.538G>A (p.Gly180Arg)

Variation ID: 3558 Accession: VCV000003558.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q12.1 16: 48224287 (GRCh38) [ NCBI UCSC ] 16: 48258198 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Apr 4, 2013	Sep 29, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001370497.1:c.538G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001357426.1:p.Gly180Arg	missense
NM_001370496.1:c.538G>A	NP_001357425.1:p.Gly180Arg	missense
NM_032583.4:c.538G>A	NP_115972.2:p.Gly180Arg	missense
NM_033151.4:c.538G>A	NP_149163.2:p.Gly180Arg	missense
NM_145186.3:c.538G>A	NP_660187.1:p.Gly180Arg	missense
NC_000016.10:g.48224287C>T
NC_000016.9:g.48258198C>T
NG_011522.1:g.15891G>A
	Q96J66:p.Gly180Arg

... more HGVS ... less HGVS

Protein change

G180R

Other names

ABCC11, GLY180ARG (rs17822931)

Canonical SPDI

NC_000016.10:48224286:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.30092 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD) 0.12273

Trans-Omics for Precision Medicine (TOPMed) 0.12976

The Genome Aggregation Database (gnomAD) 0.14076

Exome Aggregation Consortium (ExAC) 0.22511

1000 Genomes Project 30x 0.28420

1000 Genomes Project 0.30092

Links

ClinGen: CA116353 UniProtKB: Q96J66#VAR_025438 OMIM: 607040.0001 dbSNP: rs17822931 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
ABCC11		-	-	GRCh38 GRCh37	263	294

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
APOCRINE GLAND SECRETION, VARIATION IN	Benign (1)	no assertion criteria provided	Feb 28, 2011	RCV000003737.3
Axillary odor	Benign (1)	no assertion criteria provided	Feb 28, 2011	RCV000003738.2
Colostrum secretion	Benign (1)	no assertion criteria provided	Feb 28, 2011	RCV000003739.2
not provided	Benign (1)	criteria provided, single submitter	-	RCV004714398.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal dominant inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005289731.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Feb 28, 2011) N Not contributing to aggregate classification	no assertion criteria provided	APOCRINE GLAND SECRETION, VARIATION IN	OMIM Accession: SCV000023900.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (2) PubMed: 16444273‚ 19710689 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: The wet cerumen phenotype is completely dominant to the dry type (see 117800). Yoshiura et al. (2006) demonstrated that the dry ear wax phenotype is … (more) The wet cerumen phenotype is completely dominant to the dry type (see 117800). Yoshiura et al. (2006) demonstrated that the dry ear wax phenotype is recessive due to homozygous state of a 538G-A transition in exon 4 of the ABCC11 gene (rs17822931), predicting a gly180-to-arg (G180R) amino acid substitution. The AA genotype corresponds to dry ear wax, and GA and GG to the wet type. By genotyping 225 Japanese women for the rs17822931 SNP in the ABCC11 gene, Miura et al. (2007) reported an association between ear wax type and apocrine colostrum secretion (see 117800) from the mammary gland on the first postpartum day. The absence of colostrum secretion was more common among women with dry ear wax (105 of 155, 67.7%) compared to women with wet ear wax (28 of 70, 40%). The authors noted that both colostrum and cerumen have a common origin in the secretory glands and suggested that the ABCC11 gene product may play a role in colostrum secretion independent of endocrine control. Martin et al. (2010) performed chemical analysis of axillary sweat samples from 25 individuals with different ABCC11 538G-A genotypes, including 18 Asian participants (11 AA homozygotes, 5 AG heterozygotes, and 2 GG homozygotes) and 7 Caucasian participants (2 AG heterozygotes and 5 GG homozygotes). Levels of 3 glutamine conjugates that are precursors for key body odorants were below detection limits in all participants with the AA genotype but were present in all AG and GG individuals, indicating that ABCC11 is essential for secretion of amino-acid conjugates of relevant axillary odors (see 117800). RT-PCR analysis of armpit and face skin showed that ABCC11 was expressed only in the armpit specimens, suggesting that ABCC11 expression is specific to tissue containing apocrine sweat glands. Similarly, cDNA microarray analysis demonstrated 1.63-fold upregulation of ABCC11 expression in apocrine sweat glands versus 21.40-fold downregulation in eccrine sweat glands compared to a common reference. Immunohistochemistry revealed that the ABCC11 signal was concentrated in the same parts of apocrine glands in both AA and GG homozygotes, indicating that the nonfunctional ABCC11 protein is still translocated to its site of action. (less)

Benign (Feb 28, 2011) N Not contributing to aggregate classification	no assertion criteria provided	AXILLARY ODOR	OMIM Accession: SCV000023902.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (2) PubMed: 16444273‚ 19710689 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: The wet cerumen phenotype is completely dominant to the dry type (see 117800). Yoshiura et al. (2006) demonstrated that the dry ear wax phenotype is … (more) The wet cerumen phenotype is completely dominant to the dry type (see 117800). Yoshiura et al. (2006) demonstrated that the dry ear wax phenotype is recessive due to homozygous state of a 538G-A transition in exon 4 of the ABCC11 gene (rs17822931), predicting a gly180-to-arg (G180R) amino acid substitution. The AA genotype corresponds to dry ear wax, and GA and GG to the wet type. By genotyping 225 Japanese women for the rs17822931 SNP in the ABCC11 gene, Miura et al. (2007) reported an association between ear wax type and apocrine colostrum secretion (see 117800) from the mammary gland on the first postpartum day. The absence of colostrum secretion was more common among women with dry ear wax (105 of 155, 67.7%) compared to women with wet ear wax (28 of 70, 40%). The authors noted that both colostrum and cerumen have a common origin in the secretory glands and suggested that the ABCC11 gene product may play a role in colostrum secretion independent of endocrine control. Martin et al. (2010) performed chemical analysis of axillary sweat samples from 25 individuals with different ABCC11 538G-A genotypes, including 18 Asian participants (11 AA homozygotes, 5 AG heterozygotes, and 2 GG homozygotes) and 7 Caucasian participants (2 AG heterozygotes and 5 GG homozygotes). Levels of 3 glutamine conjugates that are precursors for key body odorants were below detection limits in all participants with the AA genotype but were present in all AG and GG individuals, indicating that ABCC11 is essential for secretion of amino-acid conjugates of relevant axillary odors (see 117800). RT-PCR analysis of armpit and face skin showed that ABCC11 was expressed only in the armpit specimens, suggesting that ABCC11 expression is specific to tissue containing apocrine sweat glands. Similarly, cDNA microarray analysis demonstrated 1.63-fold upregulation of ABCC11 expression in apocrine sweat glands versus 21.40-fold downregulation in eccrine sweat glands compared to a common reference. Immunohistochemistry revealed that the ABCC11 signal was concentrated in the same parts of apocrine glands in both AA and GG homozygotes, indicating that the nonfunctional ABCC11 protein is still translocated to its site of action. (less)

Benign (Feb 28, 2011) N Not contributing to aggregate classification	no assertion criteria provided	COLOSTRUM SECRETION	OMIM Accession: SCV000023903.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013	Publications: PubMed (2) PubMed: 16444273‚ 19710689 Observation: 1 Collection method: literature only Allele origin: germline Affected status: not provided more Observation 1 Collection method: literature only Allele origin: germline Affected status: not provided Comment on evidence: The wet cerumen phenotype is completely dominant to the dry type (see 117800). Yoshiura et al. (2006) demonstrated that the dry ear wax phenotype is … (more) The wet cerumen phenotype is completely dominant to the dry type (see 117800). Yoshiura et al. (2006) demonstrated that the dry ear wax phenotype is recessive due to homozygous state of a 538G-A transition in exon 4 of the ABCC11 gene (rs17822931), predicting a gly180-to-arg (G180R) amino acid substitution. The AA genotype corresponds to dry ear wax, and GA and GG to the wet type. By genotyping 225 Japanese women for the rs17822931 SNP in the ABCC11 gene, Miura et al. (2007) reported an association between ear wax type and apocrine colostrum secretion (see 117800) from the mammary gland on the first postpartum day. The absence of colostrum secretion was more common among women with dry ear wax (105 of 155, 67.7%) compared to women with wet ear wax (28 of 70, 40%). The authors noted that both colostrum and cerumen have a common origin in the secretory glands and suggested that the ABCC11 gene product may play a role in colostrum secretion independent of endocrine control. Martin et al. (2010) performed chemical analysis of axillary sweat samples from 25 individuals with different ABCC11 538G-A genotypes, including 18 Asian participants (11 AA homozygotes, 5 AG heterozygotes, and 2 GG homozygotes) and 7 Caucasian participants (2 AG heterozygotes and 5 GG homozygotes). Levels of 3 glutamine conjugates that are precursors for key body odorants were below detection limits in all participants with the AA genotype but were present in all AG and GG individuals, indicating that ABCC11 is essential for secretion of amino-acid conjugates of relevant axillary odors (see 117800). RT-PCR analysis of armpit and face skin showed that ABCC11 was expressed only in the armpit specimens, suggesting that ABCC11 expression is specific to tissue containing apocrine sweat glands. Similarly, cDNA microarray analysis demonstrated 1.63-fold upregulation of ABCC11 expression in apocrine sweat glands versus 21.40-fold downregulation in eccrine sweat glands compared to a common reference. Immunohistochemistry revealed that the ABCC11 signal was concentrated in the same parts of apocrine glands in both AA and GG homozygotes, indicating that the nonfunctional ABCC11 protein is still translocated to its site of action. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A functional ABCC11 allele is essential in the biochemical formation of human axillary odor.	Martin A	The Journal of investigative dermatology	2010	PMID: 19710689
A SNP in the ABCC11 gene is the determinant of human earwax type.	Yoshiura K	Nature genetics	2006	PMID: 16444273

Text-mined citations for rs17822931 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 17, 2025