6-25845396-G-T

Variant names:

• chr6-25845396-G-T
• NM_001098486.2:c.1483C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098486.2(SLC17A3):​c.1483C>A​(p.Leu495Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC17A3 NM_001098486.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.432

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]

LOC124901285 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06988248).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A3	NM_001098486.2	c.1483C>A	p.Leu495Ile	missense_variant	Exon 12 of 13	ENST00000397060.8	NP_001091956.1
SLC17A3	NM_006632.4	c.1249C>A	p.Leu417Ile	missense_variant	Exon 11 of 12		NP_006623.2
LOC124901285	XR_007059518.1	n.379+8864G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A3	ENST00000397060.8	c.1483C>A	p.Leu495Ile	missense_variant	Exon 12 of 13	2	NM_001098486.2	ENSP00000380250.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461704 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 727148

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	6.5
DANN	Benign	0.94
DEOGEN2	Benign	0.0043	.;.;T;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.095	N
LIST_S2	Benign	0.15	T;T;.;T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;.;L;L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.34	N;N;N;N
REVEL	Benign	0.070
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.28	T;T;T;T
Polyphen		0.40	.;.;B;B
Vest4		0.19, 0.18, 0.15
MutPred		0.19		.;.;Gain of methylation at K416 (P = 0.0477);Gain of methylation at K416 (P = 0.0477);
MVP		0.13
MPC		0.034
ClinPred		0.11	T
GERP RS		0.34
Varity_R		0.057
gMVP		0.086

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-25845624;