Variant 6-25916807-C-G 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.808G>C(p.Val270Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,614,134 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: -0.0800

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=0.0028288066).

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.808G>C	p.Val270Leu	missense_variant	8/12	ENST00000377850.8	NP_001273052.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A2	ENST00000377850.8 linkuse as main transcript	c.808G>C	p.Val270Leu	missense_variant	8/12	5	NM_001286123.3	ENSP00000367081	P1	O00624-3
SLC17A2	ENST00000360488.7 linkuse as main transcript	c.808G>C	p.Val270Leu	missense_variant	8/11	1		ENSP00000353677		O00624-2
SLC17A2	ENST00000265425.3 linkuse as main transcript	c.808G>C	p.Val270Leu	missense_variant	7/11	5		ENSP00000265425		O00624-1

Frequencies

GnomAD3 genomes

AF:

0.00160

AC:

244

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

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:

0.00221

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00141

AC:

354

AN:

251464

Hom.:

AF XY:

0.00134

AC XY:

182

AN XY:

135902

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:

2770

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00178

AC XY:

1291

AN XY:

727246

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:

0.00160

AC:

244

AN:

152250

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74444

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:

0.00221

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00181

Hom.:

Bravo

AF:

0.00177

TwinsUK

AF:

0.00378

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.808G>C (p.V270L) alteration is located in exon 8 (coding exon 7) of the SLC17A2 gene. This alteration results from a G to C substitution at nucleotide position 808, causing the valine (V) at amino acid position 270 to be replaced by a leucine (L). 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

0.090

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.4

DANN

Benign

0.22

DEOGEN2

Benign

0.11

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.68

T;T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.7

N;N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.14

N;N;N

REVEL

Benign

0.048

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010

B;.;B

Vest4

0.26

MVP

0.040

MPC

0.21

ClinPred

0.0028

GERP RS

0.93

Varity_R

0.031

gMVP

0.099

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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