Variant 6-25916997-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001286123.3(SLC17A2):c.740A>G(p.Glu247Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00187 in 1,614,142 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

SLC17A2
NM_001286123.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Variant links:

Genes affected

SLC17A2 (HGNC:10930): (solute carrier family 17 member 2) Predicted to enable sialic acid transmembrane transporter activity. Predicted to be involved in sialic acid transport. Predicted to be located in membrane. Predicted to be active in lysosome. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015440702).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A2	NM_001286123.3 linkuse as main transcript	c.740A>G	p.Glu247Gly	missense_variant	7/12	ENST00000377850.8	NP_001273052.1	O00624-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC17A2	ENST00000377850.8 linkuse as main transcript	c.740A>G	p.Glu247Gly	missense_variant	7/12	5	NM_001286123.3	ENSP00000367081.3	O00624-3
SLC17A2	ENST00000360488.7 linkuse as main transcript	c.740A>G	p.Glu247Gly	missense_variant	7/11	1		ENSP00000353677.3	O00624-2
SLC17A2	ENST00000265425.3 linkuse as main transcript	c.740A>G	p.Glu247Gly	missense_variant	6/11	5		ENSP00000265425.3	O00624-1

Frequencies

GnomAD3 genomes

AF:

0.00161

AC:

245

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00222

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00141

AC:

354

AN:

251452

Hom.:

AF XY:

0.00134

AC XY:

182

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00222

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00189

AC:

2769

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

1290

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.00248

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00151

GnomAD4 genome

AF:

0.00161

AC:

245

AN:

152326

Hom.:

Cov.:

AF XY:

0.00157

AC XY:

117

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00177

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00127

AC:

154

EpiCase

AF:

0.00213

EpiControl

AF:

0.00255

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

The c.740A>G (p.E247G) alteration is located in exon 7 (coding exon 6) of the SLC17A2 gene. This alteration results from a A to G substitution at nucleotide position 740, causing the glutamic acid (E) at amino acid position 247 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

.;.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.83

T;D;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-0.42

MutationAssessor

Uncertain

2.6

M;M;M

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-6.1

D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.92

P;.;P

Vest4

0.34

MVP

0.52

MPC

0.77

ClinPred

0.061

GERP RS

4.7

Varity_R

0.29

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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