rs33954397

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000343.4(SLC5A1):c.1938C>T(p.Asn646Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0657 in 1,613,880 control chromosomes in the GnomAD database, including 3,950 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 ( 3739 hom. )

Consequence

SLC5A1
NM_000343.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.739

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

glucose-galactose malabsorption
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SLC5A1 links:

LOC105373000 (HGNC:):

LOC105373000 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP6

Variant 22-32110156-C-T is Benign according to our data. Variant chr22-32110156-C-T is described in ClinVar as [Benign]. Clinvar id is 341267.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.739 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 rank	MANE	Protein	UniProt
SLC5A1	NM_000343.4 link	c.1938C>T	p.Asn646Asn	synonymous_variant	Exon 15 of 15	ENST00000266088.9	NP_000334.1	P13866-1
SLC5A1	NM_001256314.2 link	c.1557C>T	p.Asn519Asn	synonymous_variant	Exon 14 of 14		NP_001243243.1	P13866-2
LOC105373000	XR_938172.3 link	n.408-3214G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A1	ENST00000266088.9 link	c.1938C>T	p.Asn646Asn	synonymous_variant	Exon 15 of 15	1	NM_000343.4	ENSP00000266088.4		P13866-1
SLC5A1	ENST00000543737.2 link	c.1557C>T	p.Asn519Asn	synonymous_variant	Exon 14 of 14	2		ENSP00000444898.1		P13866-2

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6853

AN:

152132

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0343

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0377

Gnomad FIN

AF:

0.0560

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0369

GnomAD2 exomes

AF:

0.0485

AC:

12205

AN:

251404

AF XY:

0.0496

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 FIN exome

AF:

0.0517

Gnomad NFE exome

AF:

0.0705

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0679

AC:

99172

AN:

1461630

Hom.:

3739

Cov.:

AF XY:

0.0670

AC XY:

48751

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.00995

AC:

333

AN:

33478

American (AMR)

AF:

0.0318

AC:

1423

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0408

AC:

1066

AN:

26134

East Asian (EAS)

AF:

0.00186

AC:

AN:

39698

South Asian (SAS)

AF:

0.0423

AC:

3649

AN:

86256

European-Finnish (FIN)

AF:

0.0565

AC:

3019

AN:

53418

Middle Eastern (MID)

AF:

0.0316

AC:

182

AN:

5762

European-Non Finnish (NFE)

AF:

0.0773

AC:

85914

AN:

1111778

Other (OTH)

AF:

0.0582

AC:

3512

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

5044

10089

15133

20178

25222

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0450

AC:

6854

AN:

152250

Hom.:

211

Cov.:

AF XY:

0.0435

AC XY:

3236

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.0123

AC:

511

AN:

41540

American (AMR)

AF:

0.0346

AC:

529

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.0381

AC:

184

AN:

4830

European-Finnish (FIN)

AF:

0.0560

AC:

593

AN:

10592

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0706

AC:

4799

AN:

68010

Other (OTH)

AF:

0.0365

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

336

671

1007

1342

1678

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0599

Hom.:

131

Bravo

AF:

0.0428

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

5.4

(source)

DANN

Benign

0.68

PhyloP100

0.74

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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rs33954397

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over