VCV000858372.9 - ClinVar

NM_001082486.2(ACD):c.488A>G (p.Asn163Ser)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (3)

3 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_001082486.2(ACD):c.488A>G (p.Asn163Ser)

Variation ID: 858372 Accession: VCV000858372.9

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 16q22.1 16: 67659234 (GRCh38) [ NCBI UCSC ] 16: 67693137 (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 15, 2020	Mar 7, 2026	Nov 30, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001082486.2:c.488A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001075955.2:p.Asn163Ser	missense
NM_022914.3:c.479A>G	NP_075065.3:p.Asn160Ser	missense
NC_000016.10:g.67659234T>C
NC_000016.9:g.67693137T>C
NG_042874.1:g.6582A>G
NG_054728.1:g.19316T>C
LRG_1237:g.6582A>G
LRG_1237t1:c.488A>G	LRG_1237p1:p.Asn163Ser

... more HGVS ... less HGVS

Protein change

N160S, N163S

Other names

Canonical SPDI

NC_000016.10:67659233:T:C

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.

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

The Genome Aggregation Database (gnomAD), exomes 0.00007

Trans-Omics for Precision Medicine (TOPMed) 0.00007

Exome Aggregation Consortium (ExAC) 0.00009

The Genome Aggregation Database (gnomAD) 0.00009

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023

Links

ClinGen: CA8114657 dbSNP: rs370512338 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.
ACD		No evidence available	No evidence available	GRCh38 GRCh37	1263	1449

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.
Dyskeratosis congenita, autosomal dominant 6	Uncertain significance (1)	criteria provided, single submitter	Nov 30, 2025	RCV001064229.8
Long telomere syndrome	Pathogenic (1)	no assertion criteria provided	Apr 1, 2023	RCV004564545.1
not provided	Uncertain significance (1)	criteria provided, single submitter	Dec 13, 2023	RCV005232100.1
not specified	Uncertain significance (1)	criteria provided, single submitter	Mar 4, 2025	RCV005232101.1

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.
Uncertain significance (Mar 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not specified	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV005872472.1 First in ClinVar: Mar 11, 2025 Last updated: Mar 11, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain Significance (Dec 13, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV005878147.1 First in ClinVar: Mar 11, 2025 Last updated: Mar 11, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Nov 30, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Dyskeratosis congenita, autosomal dominant 6	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001229116.7 First in ClinVar: Apr 15, 2020 Last updated: Mar 07, 2026	Publications: PubMed (2) PubMed: 25505254‚ 32191290 Comment: show This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 249 of the ACD protein (p.Asn249Ser). This variant is present in population databases (rs370512338, gnomAD 0.03%). This missense change has been observed in individual(s) with cutaneous malignant melanoma and/or osteosarcoma (PMID: 25505254, 32191290). ClinVar contains an entry for this variant (Variation ID: 858372). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ACD protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Apr 01, 2023) N Not contributing to aggregate classification	no assertion criteria provided	Long telomere syndrome	The Telomere Center at Johns Hopkins, Johns Hopkins University School of Medicine Accession: SCV005049652.1 First in ClinVar: Jun 09, 2024 Last updated: Jun 09, 2024	Publications: PubMed (1) PubMed: 38688277 Observation: 1 Collection method: research Allele origin: germline Affected status: yes Observation 1 Collection method: research Allele origin: germline Affected status: yes

Comment:

This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 249 of the ACD protein (p.Asn249Ser). This variant is present in population databases (rs370512338, gnomAD 0.03%). This missense change has been observed in individual(s) with cutaneous malignant melanoma and/or osteosarcoma (PMID: 25505254, 32191290). ClinVar contains an entry for this variant (Variation ID: 858372). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ACD protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Telomere-lengthening germline variants predispose to a syndromic papillary thyroid cancer subtype.	DeBoy EA	American journal of human genetics	2024	PMID: 38688277
Frequency of Pathogenic Germline Variants in Cancer-Susceptibility Genes in Patients With Osteosarcoma.	Mirabello L	JAMA oncology	2020	PMID: 32191290
Nonsense mutations in the shelterin complex genes ACD and TERF2IP in familial melanoma.	Aoude LG	Journal of the National Cancer Institute	2014	PMID: 25505254

Text-mined citations for rs370512338 ...

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 Mar 08, 2026