6-25849936-T-C

Variant names:

• chr6-25849936-T-C
• rs141619987
• NM_001098486.2:c.1140A>G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001098486.2(SLC17A3):​c.1140A>G​(p.Ser380Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,614,082 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0019 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (19 hom.)
• Consequence: SLC17A3 NM_001098486.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.681

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-25849936-T-C is Benign according to our data. Variant chr6-25849936-T-C is described in ClinVar as [Benign]. Clinvar id is 3052099.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.681 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC17A3	NM_001098486.2	c.1140A>G	p.Ser380Ser	synonymous_variant	Exon 10 of 13	ENST00000397060.8	NP_001091956.1
SLC17A3	NM_006632.4	c.906A>G	p.Ser302Ser	synonymous_variant	Exon 9 of 12		NP_006623.2
LOC124901285	XR_007059518.1	n.380-9710T>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC17A3	ENST00000397060.8	c.1140A>G	p.Ser380Ser	synonymous_variant	Exon 10 of 13	2	NM_001098486.2	ENSP00000380250.4

Frequencies

GnomAD3 genomes AF: 0.00187 AC: 284 AN: 152216 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00851

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000764

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00214 AC: 537 AN: 251392 Hom.: 10 AF XY: 0.00212 AC XY: 288 AN XY: 135864

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00263

Gnomad ASJ exome AF: 0.0322

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000792

Gnomad OTH exome AF: 0.00440

GnomAD4 exome AF: 0.00131 AC: 1910 AN: 1461748 Hom.: 19 Cov.: 33 AF XY: 0.00129 AC XY: 941 AN XY: 727180

Gnomad4 AFR exome AF: 0.000119

Gnomad4 AMR exome AF: 0.00277

Gnomad4 ASJ exome AF: 0.0286

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000763

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.00186 AC: 284 AN: 152334 Hom.: 4 Cov.: 32 AF XY: 0.00242 AC XY: 180 AN XY: 74506

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.00850

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000765

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00311 Hom.: 3

Bravo AF: 0.00207

EpiCase AF: 0.000763

EpiControl AF: 0.00107

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

SLC17A3-related disorder Benign:1

Jul 15, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.46

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: rs141619987; hg19: chr6-25850164;