chr6-25849417-G-C

Variant names:

• chr6-25849417-G-C
• rs1581519938
• NM_001098486.2:c.1319C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001098486.2(SLC17A3):​c.1319C>G​(p.Ala440Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000116 in 1,460,710 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: SLC17A3 NM_001098486.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79
• Publications: 0 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]

LOC124901285 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.24813107).

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.1319C>G	p.Ala440Gly	missense	Exon 11 of 13	NP_001091956.1	O00476-2
	SLC17A3	NM_006632.4		c.1085C>G	p.Ala362Gly	missense	Exon 10 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.1319C>G	p.Ala440Gly	missense	Exon 11 of 13	ENSP00000380250.4	O00476-2
	SLC17A3	ENST00000361703.10	TSL:1	c.1085C>G	p.Ala362Gly	missense	Exon 10 of 12	ENSP00000355307.6	O00476-1
	SLC17A3	ENST00000861066.1		c.1319C>G	p.Ala440Gly	missense	Exon 11 of 14	ENSP00000531125.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000116 AC: 17 AN: 1460710 Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8 AN XY: 726734

African (AFR) AF: 0.00 AC: 0 AN: 33452

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39680

South Asian (SAS) AF: 0.00 AC: 0 AN: 86232

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110962

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.8
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.13
Sift	Benign	0.60	T
Sift4G	Benign	0.67	T
Polyphen		0.011	B
Vest4		0.23
MutPred		0.62		Loss of stability (P = 0.0134)
MVP		0.42
MPC		0.031
ClinPred		0.14	T
GERP RS		4.5
PromoterAI		-0.011	Neutral
Varity_R		0.089
gMVP		0.24
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1581519938; hg19: chr6-25849645;