VCV000997829.4 - ClinVar

NM_001258248.2(SP6):c.817_818delinsAT (p.Ala273Met)

Germline

Classification

no assertion criteria provided. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (2)

2 out of 2 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_001258248.2(SP6):c.817_818delinsAT (p.Ala273Met)

Variation ID: 997829 Accession: VCV000997829.4

Type and length

Indel, 2 bp

Location

Cytogenetic: 17q21.32 17: 47847612-47847613 (GRCh38) [ NCBI UCSC ] 17: 45924978-45924979 (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	Aug 26, 2021	Apr 13, 2025	Oct 27, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001258248.2:c.817_818delinsAT MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001245177.1:p.Ala273Met	missense
NM_199262.3:c.817_818delinsAT	NP_954871.1:p.Ala273Met	missense
NC_000017.11:g.47847612_47847613delinsAT
NC_000017.10:g.45924978_45924979delinsAT

Protein change

A273M

Other names

Canonical SPDI

NC_000017.11:47847611:GC:AT

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.

Links

ClinGen: CA2499224679 OMIM: 608613.0002 dbSNP: rs2143647637 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.
SP6		-	-	GRCh38 GRCh37	56	67

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.
Amelogenesis imperfecta	Pathogenic (1)	no assertion criteria provided	-	RCV001579315.5
Amelogenesis imperfecta, IIa 1K	Pathogenic (1)	no assertion criteria provided	Oct 27, 2022	RCV003329399.3

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.
Pathogenic (-) C Contributing to aggregate classification	no assertion criteria provided	Amelogenesis imperfecta (Sporadic)	Dental Genetics Laboratory, Seoul National University School of Dentistry Accession: SCV001481807.2 First in ClinVar: Aug 26, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: research Allele origin: de novo Affected status: yes more Observation 1 Collection method: research Allele origin: de novo Affected status: yes Sex: male Ethnicity/Population group: Korean Geographic origin: Republic of Korea

Pathogenic (Oct 27, 2022) C Contributing to aggregate classification	no assertion criteria provided	AMELOGENESIS IMPERFECTA, TYPE 1K	OMIM Accession: SCV002587072.2 First in ClinVar: Oct 29, 2022 Last updated: Sep 30, 2023	Publications: PubMed (1) PubMed: 33652941 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: In a 9-year-old Korean boy with hypoplastic amelogenesis imperfecta type 1K (AI1K; 620104), Kim et al. (2021) identified a de novo heterozygous deletion/insertion mutation (c.817_818delinsAT, … (more) In a 9-year-old Korean boy with hypoplastic amelogenesis imperfecta type 1K (AI1K; 620104), Kim et al. (2021) identified a de novo heterozygous deletion/insertion mutation (c.817_818delinsAT, NM_1999262.3) in the SP6 gene, predicted to result in an ala273-to-met (A273M) substitution. The mutation was identified by trio whole-exome sequencing and confirmed by Sanger sequencing. Western blot analysis and RT-PCR showed weak expression of mutant Sp6 protein compared to wildtype, but comparable expression of wildtype and mutant mRNA. The variant was not present in the gnomAD database. (less)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
A Novel De Novo SP6 Mutation Causes Severe Hypoplastic Amelogenesis Imperfecta.	Kim YJ	Genes	2021	PMID: 33652941

Text-mined citations for rs2143647637 ...

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 Apr 13, 2025