NM_030777.4(SLC2A10):c.674G>A (p.Arg225His) AND not specified

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Jan 15, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000338554.15

Allele description [Variation Report for NM_030777.4(SLC2A10):c.674G>A (p.Arg225His)]

NM_030777.4(SLC2A10):c.674G>A (p.Arg225His)

Gene:

SLC2A10:solute carrier family 2 member 10 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.12

Genomic location:

Preferred name:

NM_030777.4(SLC2A10):c.674G>A (p.Arg225His)

HGVS:

NC_000020.11:g.46725710G>A
NG_016284.1:g.21071G>A
NM_030777.4:c.674G>AMANE SELECT
NP_110404.1:p.Arg225His
NC_000020.10:g.45354349G>A
NM_030777.3:c.674G>A
O95528:p.Arg225His

Protein change:

R225H

Links:

UniProtKB: O95528#VAR_042419; dbSNP: rs34295241

NCBI 1000 Genomes Browser:

rs34295241

Molecular consequence:

NM_030777.4:c.674G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Chain H, alkyl hydroperoxide reductase C
Chain H, alkyl hydroperoxide reductase C
gi|62738239|pdb|1WE0|H

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000333791	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Aug 28, 2015)	germline	clinical testing	Citation Link,
SCV000514668	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Jul 29, 2015)	germline	clinical testing	Citation Link,
SCV001339252	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Jan 15, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001807502	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Benign	germline	clinical testing

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Arterial tortuosity syndrome: 40 new families and literature review.

Beyens A, Albuisson J, Boel A, Al-Essa M, Al-Manea W, Bonnet D, Bostan O, Boute O, Busa T, Canham N, Cil E, Coucke PJ, Cousin MA, Dasouki M, De Backer J, De Paepe A, De Schepper S, De Silva D, Devriendt K, De Wandele I, Deyle DR, Dietz H, et al.

Genet Med. 2018 Oct;20(10):1236-1245. doi: 10.1038/gim.2017.253. Epub 2018 Jan 11. Erratum in: Genet Med. 2019 Aug;21(8):1894-1895. doi: 10.1038/s41436-018-0035-3.

PubMed [citation]

PMID:: 29323665

Details of each submission

From Eurofins Ntd Llc (ga), SCV000333791.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From GeneDx, SCV000514668.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001339252.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: SLC2A10 c.674G>A (p.Arg225His) results in a non-conservative amino acid change located in the Major facilitator superfamily domain (IPR020846) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0015 in 250864 control chromosomes, including 3 homozygotes, predominantly at a frequency of 0.0089 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 5.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Arterial Tortuosity Syndrome phenotype (0.0016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.674G>A has been reported in the literature in at least one homozygous individual affected with Arterial Tortuosity Syndrome (e.g., Beyens_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Arterial Tortuosity Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 29323665). ClinVar contains an entry for this variant (Variation ID: 241606). Based on the evidence outlined above, the variant was classified as likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807502.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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