rs2235491

chr20-46725652-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030777.4(SLC2A10):c.616G>A(p.Ala206Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,613,864 control chromosomes in the GnomAD database, including 6,860 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A206V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.12 (1854 hom., cov: 33)
  • Exomes 𝑓: 0.062 (5006 hom.)
• Consequence: SLC2A10 NM_030777.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.109

Genes affected

SLC2A10 (HGNC:13444): (solute carrier family 2 member 10) This gene encodes a member of the class III facilitative glucose transporter family. The encoded protein plays a role in regulation of glucose homeostasis. Mutations in this gene have been associated with arterial tortuosity syndrome.[provided by RefSeq, Dec 2009]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038325489).
• BP6: Variant 20-46725652-G-A is Benign according to our data. Variant chr20-46725652-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 139172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46725652-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC2A10	NM_030777.4	c.616G>A	p.Ala206Thr	missense_variant	2/5	ENST00000359271.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC2A10	ENST00000359271.4	c.616G>A	p.Ala206Thr	missense_variant	2/5	1	NM_030777.4	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18537 AN: 152056 Hom.: 1845 Cov.: 33

Gnomad AFR AF: 0.263

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0392

Gnomad EAS AF: 0.0885

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0443

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.102 AC: 25546 AN: 250984 Hom.: 2168 AF XY: 0.0953 AC XY: 12938 AN XY: 135750

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.227

Gnomad ASJ exome AF: 0.0329

Gnomad EAS exome AF: 0.0838

Gnomad SAS exome AF: 0.150

Gnomad FIN exome AF: 0.0700

Gnomad NFE exome AF: 0.0429

Gnomad OTH exome AF: 0.0769

GnomAD4 exome AF: 0.0616 AC: 90031 AN: 1461690 Hom.: 5006 Cov.: 33 AF XY: 0.0629 AC XY: 45711 AN XY: 727126

Gnomad4 AFR exome AF: 0.272

Gnomad4 AMR exome AF: 0.221

Gnomad4 ASJ exome AF: 0.0334

Gnomad4 EAS exome AF: 0.0700

Gnomad4 SAS exome AF: 0.150

Gnomad4 FIN exome AF: 0.0710

Gnomad4 NFE exome AF: 0.0409

Gnomad4 OTH exome AF: 0.0753

GnomAD4 genome AF: 0.122 AC: 18573 AN: 152174 Hom.: 1854 Cov.: 33 AF XY: 0.124 AC XY: 9213 AN XY: 74392

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.149

Gnomad4 ASJ AF: 0.0392

Gnomad4 EAS AF: 0.0889

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0729

Gnomad4 NFE AF: 0.0444

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0546 Hom.: 612

Bravo AF: 0.132

TwinsUK AF: 0.0396 AC: 147

ALSPAC AF: 0.0392 AC: 151

ESP6500AA AF: 0.261 AC: 1151

ESP6500EA AF: 0.0441 AC: 379

ExAC AF: 0.101 AC: 12212

Asia WGS AF: 0.147 AC: 511 AN: 3478

EpiCase AF: 0.0449

EpiControl AF: 0.0421

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 30, 2012	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. -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Sep 24, 2020	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 06, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jan 13, 2015	p.Ala206Thr in exon 2 of SLC2A10: This variant is not expected to have clinical significance because it has been identified in 26.1% (1151/4406) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs2235491). -

Arterial tortuosity syndrome Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 29, 2016

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	7.5
Dann	Benign	0.91
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.58	T
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.090	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.10
Sift	Benign	0.58	T
Sift4G	Benign	0.24	T
Polyphen		0.0010	B
Vest4		0.016
MPC		0.065
ClinPred		0.00065	T
GERP RS		-0.60
Varity_R		0.029
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2235491; hg19: chr20-45354291; COSMIC: COSV63714167; COSMIC: COSV63714167;