rs387907257

Positions:

• chr6-25862334-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1 PM2 PP3

The NM_001098486.2(SLC17A3):​c.202A>C​(p.Asn68His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A3 NM_001098486.2 missense
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 2.54

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity NPT4_HUMAN
• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.795

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A3	NM_001098486.2	c.202A>C	p.Asn68His	missense_variant	3/13	ENST00000397060.8	NP_001091956.1
SLC17A3	NM_006632.4	c.202A>C	p.Asn68His	missense_variant	3/12		NP_006623.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A3	ENST00000397060.8	c.202A>C	p.Asn68His	missense_variant	3/13	2	NM_001098486.2	ENSP00000380250	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Uric acid concentration, serum, quantitative trait locus 4 Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Nov 05, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	.;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.85	T;.;D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.80	D;D;D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.7	M;M;M
MutationTaster	Benign	0.50	N;N;N
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.63
MutPred		0.57		Gain of glycosylation at S69 (P = 0.1295);Gain of glycosylation at S69 (P = 0.1295);Gain of glycosylation at S69 (P = 0.1295);
MVP		0.87
MPC		0.24
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.35
gMVP		0.47

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

Other links and lift over

dbSNP: rs387907257; hg19: chr6-25862562;