rs7348121

Positions:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030777.4(SLC2A10):c.1609A>G(p.Ile537Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,614,052 control chromosomes in the GnomAD database, including 205 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 Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 86 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 119 hom. )

Consequence

SLC2A10
NM_030777.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.23

Variant links:

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]

SLC2A10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003716439).

BP6

Variant 20-46733817-A-G is Benign according to our data. Variant chr20-46733817-A-G is described in ClinVar as [Benign]. Clinvar id is 139182.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-46733817-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A10	NM_030777.4 linkuse as main transcript	c.1609A>G	p.Ile537Val	missense_variant	5/5	ENST00000359271.4	NP_110404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A10	ENST00000359271.4 linkuse as main transcript	c.1609A>G	p.Ile537Val	missense_variant	5/5	1	NM_030777.4	ENSP00000352216	P1

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2956

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0654

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00648

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.000964

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.0129

GnomAD3 exomes

AF:

0.00610

AC:

1533

AN:

251458

Hom.:

AF XY:

0.00464

AC XY:

630

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0672

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.0150

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000695

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00271

AC:

3965

AN:

1461832

Hom.:

119

Cov.:

AF XY:

0.00247

AC XY:

1799

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0693

Gnomad4 AMR exome

AF:

0.00445

Gnomad4 ASJ exome

AF:

0.0144

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00118

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000429

Gnomad4 OTH exome

AF:

0.00715

GnomAD4 genome

AF:

0.0197

AC:

2997

AN:

152220

Hom.:

Cov.:

AF XY:

0.0190

AC XY:

1416

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.0663

Gnomad4 AMR

AF:

0.00647

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.000966

Gnomad4 SAS

AF:

0.00229

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.00514

Hom.:

Bravo

AF:

0.0211

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0631

AC:

278

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00704

AC:

855

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Feb 17, 2020	Variant summary: SLC2A10 c.1609A>G (p.Ile537Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0061 in 251458 control chromosomes, predominantly at a frequency of 0.067 within the African or African-American subpopulation in the gnomAD database, including 46 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 42-fold of the estimated maximal expected allele frequency for a pathogenic variant in SLC2A10 causing Aortopathy phenotype (0.0016), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1609A>G in individuals affected with Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 2013	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	PreventionGenetics, part of Exact Sciences	-	- -

Arterial tortuosity syndrome

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 13, 2020	- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:2

Benign, criteria provided, single submitter	clinical testing	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	Mar 18, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Feb 03, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.4

DANN

Benign

0.11

DEOGEN2

Benign

0.065

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.00020

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0037

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.55

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.080

REVEL

Benign

0.16

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.038

MVP

0.41

MPC

0.056

ClinPred

0.0013

GERP RS

1.8

Varity_R

0.024

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over