Variant chr6-25798909-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005074.5(SLC17A1):c.1280C>G(p.Ser427Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000007 in 1,428,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 7.0e-7 ( 0 hom. )

Consequence

SLC17A1
NM_005074.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.543

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24895865).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC17A1	NM_005074.5 linkuse as main transcript	c.1280C>G	p.Ser427Cys	missense_variant	12/13	ENST00000244527.10	NP_005065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC17A1	ENST00000244527.10 linkuse as main transcript	c.1280C>G	p.Ser427Cys	missense_variant	12/13	5	NM_005074.5	ENSP00000244527	P1	Q14916-1
SLC17A1	ENST00000468082.1 linkuse as main transcript	c.1118C>G	p.Ser373Cys	missense_variant	10/10	1		ENSP00000420546		Q14916-2
SLC17A1	ENST00000476801.5 linkuse as main transcript	c.1280C>G	p.Ser427Cys	missense_variant	12/12	2		ENSP00000420614	P1	Q14916-1
SLC17A1	ENST00000377886.6 linkuse as main transcript	c.*531C>G		3_prime_UTR_variant, NMD_transcript_variant	11/12	5		ENSP00000367118

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.00e-7

AC:

AN:

1428344

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706106

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000170

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

May 03, 2023

The c.1280C>G (p.S427C) alteration is located in exon 12 (coding exon 11) of the SLC17A1 gene. This alteration results from a C to G substitution at nucleotide position 1280, causing the serine (S) at amino acid position 427 to be replaced by a cysteine (C). 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

Benign

0.15

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.11

T;T;.

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.61

.;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.8

M;M;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.2

N;N;N

REVEL

Benign

0.19

Sift

Benign

0.086

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.43

MutPred

0.53

Loss of disorder (P = 0.0627);Loss of disorder (P = 0.0627);.;

MVP

0.67

MPC

0.38

ClinPred

0.47

GERP RS

-0.34

Varity_R

0.073

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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