Variant chr6-25849462-T-C 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.1274A>G(p.Tyr425Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,447,228 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SLC17A3
NM_001098486.2 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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:

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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.1274A>G	p.Tyr425Cys	missense_variant, splice_region_variant	11/13	ENST00000397060.8
LOC124901285	XR_007059518.1 linkuse as main transcript	n.380-10184T>C		intron_variant, non_coding_transcript_variant
SLC17A3	NM_006632.4 linkuse as main transcript	c.1040A>G	p.Tyr347Cys	missense_variant, splice_region_variant	10/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A3	ENST00000397060.8 linkuse as main transcript	c.1274A>G	p.Tyr425Cys	missense_variant, splice_region_variant	11/13	2	NM_001098486.2	P1	O00476-2
SLC17A3	ENST00000361703.10 linkuse as main transcript	c.1040A>G	p.Tyr347Cys	missense_variant, splice_region_variant	10/12	1			O00476-1
SLC17A3	ENST00000360657.7 linkuse as main transcript	c.1040A>G	p.Tyr347Cys	missense_variant, splice_region_variant	10/12	2			O00476-1
SLC17A3	ENST00000481949.6 linkuse as main transcript	c.77A>G	p.Tyr26Cys	missense_variant, splice_region_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000415

AC:

AN:

1447228

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721026

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000455

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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 14, 2021

The c.1040A>G (p.Y347C) alteration is located in exon 10 (coding exon 9) of the SLC17A3 gene. This alteration results from a A to G substitution at nucleotide position 1040, causing the tyrosine (Y) at amino acid position 347 to be replaced by a cysteine (C). 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

Uncertain

0.37

BayesDel_addAF

Benign

0.011

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.39

.;T;T

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.051

FATHMM_MKL

Benign

0.072

LIST_S2

Uncertain

0.92

D;.;D

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.60

D;D;D

MetaSVM

Benign

-0.85

MutationAssessor

Pathogenic

3.4

.;M;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-8.0

D;D;D

REVEL

Benign

0.19

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.45

MutPred

0.75

.;Loss of disorder (P = 0.1781);Loss of disorder (P = 0.1781);

MVP

0.61

MPC

0.26

ClinPred

0.96

GERP RS

3.1

Varity_R

0.50

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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