Variant 6-25811704-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005074.5(SLC17A1):c.964T>C(p.Ser322Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,613,600 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000087 ( 0 hom. )

Consequence

SLC17A1
NM_005074.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.435

Variant links:

Genes affected

SLC17A1 (HGNC:10929): (solute carrier family 17 member 1) Predicted to enable sialic acid transmembrane transporter activity. Involved in urate metabolic process and urate transport. Located in apical plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC17A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC17A1	NM_005074.5 linkuse as main transcript	c.964T>C	p.Ser322Pro	missense_variant	9/13	ENST00000244527.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC17A1	ENST00000244527.10 linkuse as main transcript	c.964T>C	p.Ser322Pro	missense_variant	9/13	5	NM_005074.5	P1	Q14916-1
SLC17A1	ENST00000468082.1 linkuse as main transcript	c.802T>C	p.Ser268Pro	missense_variant	7/10	1			Q14916-2
SLC17A1	ENST00000476801.5 linkuse as main transcript	c.964T>C	p.Ser322Pro	missense_variant	9/12	2		P1	Q14916-1
SLC17A1	ENST00000377886.6 linkuse as main transcript	c.*215T>C		3_prime_UTR_variant, NMD_transcript_variant	8/12	5

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000116

AC:

AN:

251058

Hom.:

AF XY:

0.000118

AC XY:

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000869

AC:

127

AN:

1461452

Hom.:

Cov.:

AF XY:

0.0000977

AC XY:

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.000468

Gnomad4 NFE exome

AF:

0.0000873

Gnomad4 OTH exome

AF:

0.0000828

GnomAD4 genome

AF:

0.000217

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000175

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000233

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 19, 2022

The c.964T>C (p.S322P) alteration is located in exon 9 (coding exon 8) of the SLC17A1 gene. This alteration results from a T to C substitution at nucleotide position 964, causing the serine (S) at amino acid position 322 to be replaced by a proline (P). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Uncertain

0.58

D;D;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.017

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.59

D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-2.5

N;N;N

REVEL

Uncertain

0.35

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.85

P;P;P

Vest4

0.70

MVP

0.59

MPC

0.49

ClinPred

0.26

GERP RS

-6.8

Varity_R

0.87

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over