6-25850620-C-T

Position:

• chr6-25850620-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098486.2(SLC17A3):​c.832G>A​(p.Val278Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,714 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 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: 0.0000048 (0 hom.)
• Consequence: SLC17A3 NM_001098486.2 missense, splice_region
• Scores: Splicing: ADA: 0.005382
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.859

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039266586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A3	NM_001098486.2	c.832G>A	p.Val278Ile	missense_variant, splice_region_variant	8/13	ENST00000397060.8
LOC124901285	XR_007059518.1	n.380-9026C>T		intron_variant, non_coding_transcript_variant
SLC17A3	NM_006632.4	c.598G>A	p.Val200Ile	missense_variant, splice_region_variant	7/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A3	ENST00000397060.8	c.832G>A	p.Val278Ile	missense_variant, splice_region_variant	8/13	2	NM_001098486.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461714 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727150

Gnomad4 AFR exome AF: 0.000119

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.598G>A (p.V200I) alteration is located in exon 7 (coding exon 6) of the SLC17A3 gene. This alteration results from a G to A substitution at nucleotide position 598, causing the valine (V) at amino acid position 200 to be replaced by an isoleucine (I). 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	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.042	.;T;T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.25	T;.;T
M_CAP	Benign	0.0036	T
MetaRNN	Benign	0.039	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.36	N;N;N
REVEL	Benign	0.11
Sift	Benign	0.37	T;T;T
Sift4G	Benign	0.36	T;T;T
Polyphen		0.89	.;P;P
Vest4		0.067
MutPred		0.33		.;Loss of helix (P = 0.1299);Loss of helix (P = 0.1299);
MVP		0.32
MPC		0.043
ClinPred		0.27	T
GERP RS		0.42
Varity_R		0.039
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0054
dbscSNV1_RF	Benign	0.19
SpliceAI score (max)		0.12		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: rs1765259423; hg19: chr6-25850848;