Variant 6-25849392-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001098486.2(SLC17A3):c.1344T>A(p.Ser448Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,607,540 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SLC17A3
NM_001098486.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.632

Variant links:

Genes affected

SLC17A3 (HGNC:10931): (solute carrier family 17 member 3) The protein encoded by this gene is a voltage-driven transporter that excretes intracellular urate and organic anions from the blood into renal tubule cells. Two transcript variants encoding different isoforms have been found for this gene. The longer isoform is a plasma membrane protein with transporter activity while the shorter isoform localizes to the endoplasmic reticulum. [provided by RefSeq, Aug 2012]

SLC17A3 links:

LOC124901285 (HGNC:):

LOC124901285 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC17A3	NM_001098486.2 linkuse as main transcript	c.1344T>A	p.Ser448Arg	missense_variant	11/13	ENST00000397060.8
LOC124901285	XR_007059518.1 linkuse as main transcript	n.380-10254A>T		intron_variant, non_coding_transcript_variant
SLC17A3	NM_006632.4 linkuse as main transcript	c.1110T>A	p.Ser370Arg	missense_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A3	ENST00000397060.8 linkuse as main transcript	c.1344T>A	p.Ser448Arg	missense_variant	11/13	2	NM_001098486.2	P1	O00476-2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455660

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151880

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74160

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

7.2

DANN

Benign

0.95

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.028

LIST_S2

Uncertain

0.90

D;T;.;T

M_CAP

Benign

0.015

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-2.4

N;D;D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0060

D;D;D;D

Sift4G

Uncertain

0.049

D;D;D;D

Polyphen

0.84

.;.;P;P

Vest4

0.50, 0.54, 0.52

MutPred

0.75

.;.;Gain of methylation at S370 (P = 0.01);Gain of methylation at S370 (P = 0.01);

MVP

0.44

MPC

0.072

ClinPred

0.38

GERP RS

-0.84

Varity_R

0.20

gMVP

0.73

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over