rs33954397

Variant names:

• chr22-32110156-C-T
• rs33954397
• NM_000343.4:c.1938C>T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.739

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]

LOC105373000 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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	c.1938C>T	p.Asn646Asn	synonymous_variant	Exon 15 of 15	ENST00000266088.9	NP_000334.1
SLC5A1	NM_001256314.2	c.1557C>T	p.Asn519Asn	synonymous_variant	Exon 14 of 14		NP_001243243.1
LOC105373000	XR_938172.3	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	c.1938C>T	p.Asn646Asn	synonymous_variant	Exon 15 of 15	1	NM_000343.4	ENSP00000266088.4
SLC5A1	ENST00000543737.2	c.1557C>T	p.Asn519Asn	synonymous_variant	Exon 14 of 14	2		ENSP00000444898.1

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6853 AN: 152132 Hom.: 212 Cov.: 32

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

GnomAD3 exomes AF: 0.0485 AC: 12205 AN: 251404 Hom.: 386 AF XY: 0.0496 AC XY: 6734 AN XY: 135870

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: 0.0389

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.: 32 AF XY: 0.0670 AC XY: 48751 AN XY: 727126

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: 0.0423

Gnomad4 FIN exome AF: 0.0565

Gnomad4 NFE exome AF: 0.0773

Gnomad4 OTH exome AF: 0.0582

GnomAD4 genome AF: 0.0450 AC: 6854 AN: 152250 Hom.: 211 Cov.: 32 AF XY: 0.0435 AC XY: 3236 AN XY: 74448

Gnomad4 AFR AF: 0.0123

Gnomad4 AMR AF: 0.0346

Gnomad4 ASJ AF: 0.0412

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0381

Gnomad4 FIN AF: 0.0560

Gnomad4 NFE AF: 0.0706

Gnomad4 OTH AF: 0.0365

Alfa AF: 0.0604 Hom.: 131

Bravo AF: 0.0428

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.0603

EpiControl AF: 0.0660

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital glucose-galactose malabsorption Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

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
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs33954397; hg19: chr22-32506143; COSMIC: COSV56683033;