NM_001098486.2:c.1407C>T

Variant names:

• chr6-25845472-G-A
• rs116732075
• NM_001098486.2:c.1407C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BS1 BS2

The NM_001098486.2(SLC17A3):​c.1407C>T​(p.Ala469Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00171 in 1,613,942 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0016 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (55 hom.)
• Consequence: SLC17A3 NM_001098486.2 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.466
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• uric acid concentration, serum, quantitative trait locus 4

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

LOC124901285 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.006).
• BP6: Variant 6-25845472-G-A is Benign according to our data. Variant chr6-25845472-G-A is described in ClinVar as Benign. ClinVar VariationId is 3044906.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.466 with no splicing effect.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00164 (249/152198) while in subpopulation EAS AF = 0.0268 (139/5182). AF 95% confidence interval is 0.0232. There are 5 homozygotes in GnomAd4. There are 167 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

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.1407C>T	p.Ala469Ala	synonymous	Exon 12 of 13	NP_001091956.1	O00476-2
	SLC17A3	NM_006632.4		c.1173C>T	p.Ala391Ala	synonymous	Exon 11 of 12	NP_006623.2	O00476-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC17A3	ENST00000397060.8	TSL:2 MANE Select	c.1407C>T	p.Ala469Ala	synonymous	Exon 12 of 13	ENSP00000380250.4	O00476-2
	SLC17A3	ENST00000361703.10	TSL:1	c.1173C>T	p.Ala391Ala	synonymous	Exon 11 of 12	ENSP00000355307.6	O00476-1
	SLC17A3	ENST00000861066.1		c.1407C>T	p.Ala469Ala	synonymous	Exon 12 of 14	ENSP00000531125.1

Frequencies

GnomAD3 genomes AF: 0.00165 AC: 251 AN: 152080 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0271

Gnomad SAS AF: 0.0201

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00541 AC: 1359 AN: 251312 AF XY: 0.00618

Gnomad AFR exome AF: 0.000246

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0420

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00172 AC: 2516 AN: 1461744 Hom.: 55 Cov.: 31 AF XY: 0.00226 AC XY: 1643 AN XY: 727168

African (AFR) AF: 0.000329 AC: 11 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0163 AC: 647 AN: 39676

South Asian (SAS) AF: 0.0188 AC: 1619 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00139 AC: 8 AN: 5764

European-Non Finnish (NFE) AF: 0.0000486 AC: 54 AN: 1111922

Other (OTH) AF: 0.00288 AC: 174 AN: 60390

GnomAD4 genome AF: 0.00164 AC: 249 AN: 152198 Hom.: 5 Cov.: 32 AF XY: 0.00224 AC XY: 167 AN XY: 74410

African (AFR) AF: 0.000144 AC: 6 AN: 41524

American (AMR) AF: 0.000196 AC: 3 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0268 AC: 139 AN: 5182

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68014

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.000261 Hom.: 0

Bravo AF: 0.00164

Asia WGS AF: 0.0170 AC: 60 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SLC17A3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs116732075; hg19: chr6-25845700;