rs387907256

Variant names:

• chr6-25850541-A-G
• rs387907256
• NM_001098486.2:c.911T>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001098486.2(SLC17A3):​c.911T>C​(p.Phe304Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as association (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC17A3 NM_001098486.2 missense
• Clinical Significance: association no assertion criteria provided O:1
• Conservation: PhyloP100: 2.77
• 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.856

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.911T>C	p.Phe304Ser	missense	Exon 8 of 13	NP_001091956.1	O00476-2
	SLC17A3	NM_006632.4		c.677T>C	p.Phe226Ser	missense	Exon 7 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.911T>C	p.Phe304Ser	missense	Exon 8 of 13	ENSP00000380250.4	O00476-2
	SLC17A3	ENST00000361703.10	TSL:1	c.677T>C	p.Phe226Ser	missense	Exon 7 of 12	ENSP00000355307.6	O00476-1
	SLC17A3	ENST00000861066.1		c.911T>C	p.Phe304Ser	missense	Exon 8 of 14	ENSP00000531125.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: association

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Uric acid concentration, serum, quantitative trait locus 4 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.0058
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.055	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.80	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.8
PrimateAI	Benign	0.48	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.89
MutPred		0.67		Loss of helix (P = 0.2271)
MVP		0.71
MPC		0.28
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.50
gMVP		0.59
Mutation Taster		=7/93	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs387907256; hg19: chr6-25850769;