chr20-46725710-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_030777.4(SLC2A10):c.674G>A(p.Arg225His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000915 in 1,614,086 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R225C) has been classified as Uncertain significance.
Frequency
Consequence
NM_030777.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC2A10 | NM_030777.4 | c.674G>A | p.Arg225His | missense_variant | 2/5 | ENST00000359271.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC2A10 | ENST00000359271.4 | c.674G>A | p.Arg225His | missense_variant | 2/5 | 1 | NM_030777.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00303 AC: 461AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00147 AC: 369AN: 250864Hom.: 3 AF XY: 0.00164 AC XY: 222AN XY: 135686
GnomAD4 exome AF: 0.000695 AC: 1016AN: 1461778Hom.: 9 Cov.: 33 AF XY: 0.000839 AC XY: 610AN XY: 727200
GnomAD4 genome AF: 0.00303 AC: 461AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.00301 AC XY: 224AN XY: 74462
ClinVar
Submissions by phenotype
not specified Benign:4
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 29, 2015 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 28, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jan 15, 2024 | 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. - |
not provided Uncertain:1Benign:1
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2017 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 20, 2015 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | May 01, 2019 | - - |
Arterial tortuosity syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 25, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at