Genetic Variant NM_001098486.2:c.1490G>T (chr6-25845389-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001098486.2(SLC17A3):c.1490G>T(p.Arg497Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R497C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

SLC17A3
NM_001098486.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.832

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1628311).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098486.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A3	NM_001098486.2	MANE Select	c.1490G>T	p.Arg497Leu	missense	Exon 12 of 13	NP_001091956.1	O00476-2
	SLC17A3	NM_006632.4		c.1256G>T	p.Arg419Leu	missense	Exon 11 of 12	NP_006623.2	O00476-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC17A3	ENST00000397060.8	TSL:2 MANE Select	c.1490G>T	p.Arg497Leu	missense	Exon 12 of 13	ENSP00000380250.4	O00476-2
SLC17A3	ENST00000361703.10	TSL:1	c.1256G>T	p.Arg419Leu	missense	Exon 11 of 12	ENSP00000355307.6	O00476-1
SLC17A3	ENST00000861066.1		c.1490G>T	p.Arg497Leu	missense	Exon 12 of 14	ENSP00000531125.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251296

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000173

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461658

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727118

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.000157

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111860

Other (OTH)

AF:

0.00

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.73

M_CAP

Benign

0.036

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.7

PhyloP100

-0.83

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-4.4

REVEL

Benign

0.16

Sift

Uncertain

0.0090

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.48

MutPred

0.35

Loss of MoRF binding (P = 0.0148)

MVP

0.34

MPC

0.16

ClinPred

0.67

GERP RS

0.81

Varity_R

0.19

gMVP

0.47

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over