rs17683430

Positions:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 3P and 20B. PM1PP2BP4_StrongBP6_Very_StrongBA1

The NM_000343.4(SLC5A1):c.1231G>A(p.Ala411Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0656 in 1,613,408 control chromosomes in the GnomAD database, including 3,945 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.045 ( 207 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3738 hom. )

Consequence

SLC5A1
NM_000343.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.30

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:

SLC5A1 (HGNC:):

SLC5A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

PM1

In a disulfide_bond (size 256) in uniprot entity SC5A1_HUMAN there are 15 pathogenic changes around while only 0 benign (100%) in NM_000343.4

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC5A1. . Gene score misZ 1.833 (greater than the threshold 3.09). Trascript score misZ 3.1348 (greater than threshold 3.09). GenCC has associacion of gene with glucose-galactose malabsorption.

BP4

Computational evidence support a benign effect (MetaRNN=0.00344944).

BP6

Variant 22-32091713-G-A is Benign according to our data. Variant chr22-32091713-G-A is described in ClinVar as [Benign]. Clinvar id is 341252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A1	NM_000343.4 linkuse as main transcript	c.1231G>A	p.Ala411Thr	missense_variant	11/15	ENST00000266088.9	NP_000334.1	P13866-1
SLC5A1	NM_001256314.2 linkuse as main transcript	c.850G>A	p.Ala284Thr	missense_variant	10/14		NP_001243243.1	P13866-2
SLC5A1	XM_011530331.2 linkuse as main transcript	c.1231G>A	p.Ala411Thr	missense_variant	11/12		XP_011528633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SLC5A1	ENST00000266088.9 linkuse as main transcript	c.1231G>A	p.Ala411Thr	missense_variant	11/15	1	NM_000343.4	ENSP00000266088.4	P13866-1
SLC5A1	ENST00000543737.2 linkuse as main transcript	c.850G>A	p.Ala284Thr	missense_variant	10/14	2		ENSP00000444898.1	P13866-2
SLC5A1	ENST00000477969.1 linkuse as main transcript	n.397G>A		non_coding_transcript_exon_variant	3/5	3

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6840

AN:

151950

Hom.:

208

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00659

Gnomad AMR

AF:

0.0341

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0374

Gnomad FIN

AF:

0.0559

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0705

Gnomad OTH

AF:

0.0369

GnomAD3 exomes

AF:

0.0486

AC:

12204

AN:

251274

Hom.:

388

AF XY:

0.0496

AC XY:

6731

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0291

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.00131

Gnomad SAS exome

AF:

0.0391

Gnomad FIN exome

AF:

0.0517

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0678

AC:

99022

AN:

1461340

Hom.:

3738

Cov.:

AF XY:

0.0670

AC XY:

48693

AN XY:

727002

show subpopulations

Gnomad4 AFR exome

AF:

0.00995

Gnomad4 AMR exome

AF:

0.0318

Gnomad4 ASJ exome

AF:

0.0408

Gnomad4 EAS exome

AF:

0.00186

Gnomad4 SAS exome

AF:

0.0425

Gnomad4 FIN exome

AF:

0.0565

Gnomad4 NFE exome

AF:

0.0772

Gnomad4 OTH exome

AF:

0.0581

GnomAD4 genome

AF:

0.0450

AC:

6841

AN:

152068

Hom.:

207

Cov.:

AF XY:

0.0435

AC XY:

3229

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0123

Gnomad4 AMR

AF:

0.0344

Gnomad4 ASJ

AF:

0.0412

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0379

Gnomad4 FIN

AF:

0.0559

Gnomad4 NFE

AF:

0.0705

Gnomad4 OTH

AF:

0.0365

Alfa

AF:

0.0603

Hom.:

505

Bravo

AF:

0.0427

TwinsUK

AF:

0.0747

AC:

277

ALSPAC

AF:

0.0791

AC:

305

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0700

AC:

602

ExAC

AF:

0.0501

AC:

6079

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0603

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	Mar 06, 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

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.21

DEOGEN2

Benign

0.047

T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.1

N;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

2.2

N;N

REVEL

Benign

0.28

Sift

Benign

0.97

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.0

B;.

Vest4

0.046

MPC

0.45

ClinPred

0.0080

GERP RS

5.9

Varity_R

0.097

gMVP

0.30

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