Variant 22-32231009-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_014227.3(SLC5A4):c.1088A>G(p.Asn363Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000873 in 1,613,906 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00090 ( 4 hom. )

Consequence

SLC5A4
NM_014227.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.05

Variant links:

Genes affected

SLC5A4 (HGNC:11039): (solute carrier family 5 member 4) Predicted to enable glucose:sodium symporter activity and proton transmembrane transporter activity. Predicted to be involved in sodium ion transport. Predicted to act upstream of or within proton transmembrane transport. Predicted to be active in plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC5A4 links:

SLC5A4-AS1 (HGNC:53163): (SLC5A4 antisense RNA 1)

SLC5A4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3296578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A4	NM_014227.3 linkuse as main transcript	c.1088A>G	p.Asn363Ser	missense_variant	10/15	ENST00000266086.6
SLC5A4-AS1	NR_149072.1 linkuse as main transcript	n.274+23733T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
SLC5A4	ENST00000266086.6 linkuse as main transcript	c.1088A>G	p.Asn363Ser	missense_variant	10/15	1	NM_014227.3	P1
SLC5A4-AS1	ENST00000452181.2 linkuse as main transcript	n.274+23733T>C		intron_variant, non_coding_transcript_variant		5
SLC5A4-AS1	ENST00000434942.2 linkuse as main transcript	n.507+1637T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000585

AC:

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000648

AC:

163

AN:

251390

Hom.:

AF XY:

0.000582

AC XY:

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00259

Gnomad NFE exome

AF:

0.000836

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000903

AC:

1320

AN:

1461712

Hom.:

Cov.:

AF XY:

0.000869

AC XY:

632

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00290

Gnomad4 NFE exome

AF:

0.00100

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.000585

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000686

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000664

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.000486

AC:

EpiCase

AF:

0.00109

EpiControl

AF:

0.000593

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

Jun 29, 2022

The c.1088A>G (p.N363S) alteration is located in exon 10 (coding exon 10) of the SLC5A4 gene. This alteration results from a A to G substitution at nucleotide position 1088, causing the asparagine (N) at amino acid position 363 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.19

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Benign

0.031

Eigen_PC

Benign

0.037

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.016

MetaRNN

Benign

0.33

MetaSVM

Uncertain

0.47

MutationAssessor

Uncertain

2.7

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Uncertain

-4.0

REVEL

Uncertain

0.59

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.024

Polyphen

0.093

Vest4

0.88

MVP

0.57

MPC

0.49

ClinPred

0.092

GERP RS

3.8

Varity_R

0.51

gMVP

0.14

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