Variant 16-24897974-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001352248.3(SLC5A11):c.871G>A(p.Val291Met) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,613,898 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00092 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 3 hom. )

Consequence

SLC5A11
NM_001352248.3 missense, splice_region

Scores

Splicing: ADA: 0.9977

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.81

Variant links:

Genes affected

SLC5A11 (HGNC:23091): (solute carrier family 5 member 11) Cotransporters, such as SLC5A11, represent a major class of proteins that make use of ion gradients to drive active transport for the cellular accumulation of nutrients, neurotransmitters, osmolytes, and ions Roll et al. (2002) [PubMed 12039040].[supplied by OMIM, Mar 2008]

SLC5A11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A11	NM_001352248.3 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant, splice_region_variant	11/17	ENST00000424767.7	NP_001339177.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A11	ENST00000424767.7 linkuse as main transcript	c.871G>A	p.Val291Met	missense_variant, splice_region_variant	11/17	2	NM_001352248.3	ENSP00000416782	P1	Q8WWX8-1

Frequencies

GnomAD3 genomes

AF:

0.000920

AC:

140

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000435

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00126

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000717

AC:

180

AN:

250890

Hom.:

AF XY:

0.000671

AC XY:

AN XY:

135548

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000997

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00102

AC:

1490

AN:

1461656

Hom.:

Cov.:

AF XY:

0.000997

AC XY:

725

AN XY:

727138

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00119

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.000920

AC:

140

AN:

152242

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00126

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000949

Hom.:

Bravo

AF:

0.00102

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000576

AC:

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.000981

EpiControl

AF:

0.000949

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

Aug 02, 2021

The c.871G>A (p.V291M) alteration is located in exon 10 (coding exon 9) of the SLC5A11 gene. This alteration results from a G to A substitution at nucleotide position 871, causing the valine (V) at amino acid position 291 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

Pathogenic

0.84

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.95

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.22

T;.

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.15

T;T

MetaSVM

Pathogenic

0.86

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;N;N

PROVEAN

Benign

-1.1

N;N

REVEL

Uncertain

0.55

Sift

Benign

0.097

T;T

Sift4G

Uncertain

0.042

D;D

Vest4

0.53

MVP

0.82

ClinPred

0.089

GERP RS

5.5

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.89

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