VCV003027506.2 - ClinVar

NM_001178015.2(SLC4A10):c.1864C>T (p.Arg622Trp)

Germline

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.

(1)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001178015.2(SLC4A10):c.1864C>T (p.Arg622Trp)

Variation ID: 3027506 Accession: VCV003027506.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q24.2 2: 161905754 (GRCh38) [ NCBI UCSC ] 2: 162762264 (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	Mar 11, 2024	Mar 16, 2024	Mar 8, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001178015.2:c.1864C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001171486.1:p.Arg622Trp	missense
NM_001178016.2:c.1807C>T	NP_001171487.1:p.Arg603Trp	missense
NM_001354440.2:c.1864C>T	NP_001341369.1:p.Arg622Trp	missense
NM_001354441.2:c.1897C>T	NP_001341370.1:p.Arg633Trp	missense
NM_001354442.2:c.1897C>T	NP_001341371.1:p.Arg633Trp	missense
NM_001354443.2:c.1810C>T	NP_001341372.1:p.Arg604Trp	missense
NM_001354444.2:c.1861C>T	NP_001341373.1:p.Arg621Trp	missense
NM_001354445.2:c.1807C>T	NP_001341374.1:p.Arg603Trp	missense
NM_001354446.2:c.1774C>T	NP_001341375.1:p.Arg592Trp	missense
NM_001354447.2:c.1810C>T	NP_001341376.1:p.Arg604Trp	missense
NM_001354448.2:c.1804C>T	NP_001341377.1:p.Arg602Trp	missense
NM_001354449.2:c.1771C>T	NP_001341378.1:p.Arg591Trp	missense
NM_001354450.2:c.1774C>T	NP_001341379.1:p.Arg592Trp	missense
NM_001354451.2:c.1771C>T	NP_001341380.1:p.Arg591Trp	missense
NM_001354453.2:c.1627C>T	NP_001341382.1:p.Arg543Trp	missense
NM_001354455.2:c.1195C>T	NP_001341384.1:p.Arg399Trp	missense
NM_001354460.2:c.1900C>T	NP_001341389.1:p.Arg634Trp	missense
NM_001354461.2:c.1900C>T	NP_001341390.1:p.Arg634Trp	missense
NM_022058.4:c.1774C>T	NP_071341.2:p.Arg592Trp	missense
NC_000002.12:g.161905754C>T
NC_000002.11:g.162762264C>T
NG_021401.1:g.286420C>T

... more HGVS ... less HGVS

Protein change

R399W, R543W, R591W, R592W, R602W, R603W, R604W, R621W, R633W, R634W

Other names

R622W

Canonical SPDI

NC_000002.12:161905753:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

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

OMIM: 605556.0008 VarSome

Comment on variant

OMIM allelic variant 605556.0008 was initially processed as NM_001178016.1:c.1864C>T (reported in the text of the allelic variant) instead of NM_001178015.2:c.1864C>T as reported in Figure 1 of the paper by Maroofian et al., 2024 (PubMed 38054405).

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.
SLC4A10		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	101	127

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.
Neurodevelopmental disorder with hypotonia and characteristic brain abnormalities	Pathogenic (1)	no assertion criteria provided	Mar 8, 2024	RCV003889365.2

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.	More information 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 (Mar 08, 2024)	no assertion criteria provided Method: literature only	NEURODEVELOPMENTAL DISORDER WITH HYPOTONIA AND CHARACTERISTIC BRAIN ABNORMALITIES Affected status: not provided Allele origin: germline	OMIM Accession: SCV004704611.2 First in ClinVar: Mar 10, 2024 Last updated: Mar 16, 2024	Publications: PubMed (1) PubMed: 38054405 Comment on evidence: For discussion of the c.1864C-T transition (c.1864C-T, NM_001178016.1) in the SLC4A10 gene, resulting in an arg622-to-trp (R622W) substitution, that was identified in compound heterozygous state … (more) For discussion of the c.1864C-T transition (c.1864C-T, NM_001178016.1) in the SLC4A10 gene, resulting in an arg622-to-trp (R622W) substitution, that was identified in compound heterozygous state in a patient (family 2) with hypotonia and characteristic brain abnormalities (NEDHBA; 620746) by Maroofian et al. (2024), see 605556.0007. (less)

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Biallelic variants in SLC4A10 encoding a sodium-dependent bicarbonate transporter lead to a neurodevelopmental disorder.	Maroofian R	Genetics in medicine : official journal of the American College of Medical Genetics	2024	PMID: 38054405

Text-mined citations for this variant ...

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_001178015.2(SLC4A10):c.1864C>T (p.Arg622Trp)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...