rs17683448

Positions:

chr22-32091757-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000343.4(SLC5A1):c.1275C>T(p.Ala425=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,612,790 control chromosomes in the GnomAD database, including 3,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 211 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3746 hom. )

Consequence

SLC5A1
NM_000343.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.111

Variant links:

Genes affected

SLC5A1 (HGNC:11036): (solute carrier family 5 member 1) This gene encodes a member of the sodium-dependent glucose transporter (SGLT) family. The encoded integral membrane protein is the primary mediator of dietary glucose and galactose uptake from the intestinal lumen. Mutations in this gene have been associated with glucose-galactose malabsorption. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

SLC5A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 22-32091757-C-T is Benign according to our data. Variant chr22-32091757-C-T is described in ClinVar as [Benign]. Clinvar id is 341253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.111 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC5A1	NM_000343.4 linkuse as main transcript	c.1275C>T	p.Ala425=	synonymous_variant	11/15	ENST00000266088.9	NP_000334.1
SLC5A1	NM_001256314.2 linkuse as main transcript	c.894C>T	p.Ala298=	synonymous_variant	10/14		NP_001243243.1
SLC5A1	XM_011530331.2 linkuse as main transcript	c.1275C>T	p.Ala425=	synonymous_variant	11/12		XP_011528633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A1	ENST00000266088.9 linkuse as main transcript	c.1275C>T	p.Ala425=	synonymous_variant	11/15	1	NM_000343.4	ENSP00000266088	P1	P13866-1
SLC5A1	ENST00000543737.2 linkuse as main transcript	c.894C>T	p.Ala298=	synonymous_variant	10/14	2		ENSP00000444898		P13866-2
SLC5A1	ENST00000477969.1 linkuse as main transcript	n.441C>T		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6839

AN:

151900

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0413

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0369

GnomAD3 exomes

AF:

0.0485

AC:

12176

AN:

250988

Hom.:

386

AF XY:

0.0495

AC XY:

6714

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.00125

Gnomad SAS exome

AF:

0.0391

Gnomad FIN exome

AF:

0.0514

Gnomad NFE exome

AF:

0.0704

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0677

AC:

98908

AN:

1460772

Hom.:

3746

Cov.:

AF XY:

0.0669

AC XY:

48648

AN XY:

726762

show subpopulations

Gnomad4 AFR exome

AF:

0.00995

Gnomad4 AMR exome

AF:

0.0319

Gnomad4 ASJ exome

AF:

0.0408

Gnomad4 EAS exome

AF:

0.00184

Gnomad4 SAS exome

AF:

0.0424

Gnomad4 FIN exome

AF:

0.0564

Gnomad4 NFE exome

AF:

0.0771

Gnomad4 OTH exome

AF:

0.0580

GnomAD4 genome

AF:

0.0450

AC:

6840

AN:

152018

Hom.:

211

Cov.:

AF XY:

0.0435

AC XY:

3230

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.0347

Gnomad4 ASJ

AF:

0.0413

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0374

Gnomad4 FIN

AF:

0.0557

Gnomad4 NFE

AF:

0.0706

Gnomad4 OTH

AF:

0.0366

Alfa

AF:

0.0580

Hom.:

350

Bravo

AF:

0.0428

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0604

EpiControl

AF:

0.0660

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital glucose-galactose malabsorption

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.5

DANN

Benign

0.60

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