dbSNP rs372402739: SLC5A10:p.Val18Met (chr17-18952257-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001042450.4(SLC5A10):c.52G>A(p.Val18Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000013 ( 0 hom. )

Consequence

SLC5A10
NM_001042450.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.179

Variant links:

Genes affected

SLC5A10 (HGNC:23155): (solute carrier family 5 member 10) This gene is a member of the sodium/glucose transporter family. Members of this family are sodium-dependent transporters and can be divided into two subfamilies based on sequence homology, one that co-transports sugars and the second that transports molecules such as ascorbate, choline, iodide, lipoate, monocaroboxylates, and pantothenate. The protein encoded by this gene has the highest affinity for mannose and has been reported to be most highly expressed in the kidney. This protein may function as a kidney-specific, sodium-dependent mannose and fructose co-transporter. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

SLC5A10 links:

ENSG00000196893 (HGNC:):

ENSG00000196893 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=0.12494099).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A10	NM_001042450.4 link	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 15	ENST00000395645.4	NP_001035915.1	A0PJK1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A10	ENST00000395645.4 link	c.52G>A	p.Val18Met	missense_variant	Exon 1 of 15	1	NM_001042450.4	ENSP00000379007.3		A0PJK1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248400

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461680

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000151

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.52G>A (p.V18M) alteration is located in exon 1 (coding exon 1) of the SLC5A10 gene. This alteration results from a G to A substitution at nucleotide position 52, causing the valine (V) at amino acid position 18 to be replaced by a methionine (M). 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

0.088

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

.;.;.;T

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.51

T;T;T;T

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.5

M;M;M;M

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Benign

0.14

Sift

Benign

0.038

D;D;D;D

Sift4G

Benign

0.066

T;T;T;T

Polyphen

0.098

B;.;B;B

Vest4

0.064

MutPred

0.45

Gain of disorder (P = 0.0956);Gain of disorder (P = 0.0956);Gain of disorder (P = 0.0956);Gain of disorder (P = 0.0956);

MVP

0.33

MPC

0.22

ClinPred

0.24

GERP RS

2.1

Varity_R

0.041

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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