rs33943816

chr22-32110117-G-Achr22-32110117-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000343.4(SLC5A1):c.1899G>A(p.Thr633=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,613,924 control chromosomes in the GnomAD database, including 2,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (180 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2752 hom.)
• Consequence: SLC5A1 NM_000343.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.37

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 22-32110117-G-A is Benign according to our data. Variant chr22-32110117-G-A is described in ClinVar as [Benign]. Clinvar id is 341265.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A1	NM_000343.4	c.1899G>A	p.Thr633=	synonymous_variant	15/15	ENST00000266088.9
LOC105373000	XR_938172.3	n.408-3175C>T		intron_variant, non_coding_transcript_variant
SLC5A1	NM_001256314.2	c.1518G>A	p.Thr506=	synonymous_variant	14/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A1	ENST00000266088.9	c.1899G>A	p.Thr633=	synonymous_variant	15/15	1	NM_000343.4	P1
SLC5A1	ENST00000543737.2	c.1518G>A	p.Thr506=	synonymous_variant	14/14	2

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6454 AN: 152134 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.0204

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0602

Gnomad OTH AF: 0.0598

GnomAD3 exomes AF: 0.0461 AC: 11587 AN: 251432 Hom.: 340 AF XY: 0.0478 AC XY: 6500 AN XY: 135882

Gnomad AFR exome AF: 0.00960

Gnomad AMR exome AF: 0.0371

Gnomad ASJ exome AF: 0.0994

Gnomad EAS exome AF: 0.0208

Gnomad SAS exome AF: 0.0450

Gnomad FIN exome AF: 0.0192

Gnomad NFE exome AF: 0.0581

Gnomad OTH exome AF: 0.0593

GnomAD4 exome AF: 0.0585 AC: 85463 AN: 1461672 Hom.: 2752 Cov.: 32 AF XY: 0.0582 AC XY: 42348 AN XY: 727136

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.0380

Gnomad4 ASJ exome AF: 0.0998

Gnomad4 EAS exome AF: 0.0147

Gnomad4 SAS exome AF: 0.0451

Gnomad4 FIN exome AF: 0.0207

Gnomad4 NFE exome AF: 0.0638

Gnomad4 OTH exome AF: 0.0627

GnomAD4 genome AF: 0.0424 AC: 6459 AN: 152252 Hom.: 180 Cov.: 32 AF XY: 0.0408 AC XY: 3036 AN XY: 74444

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0567

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.0206

Gnomad4 SAS AF: 0.0439

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0602

Gnomad4 OTH AF: 0.0620

Alfa AF: 0.0477 Hom.: 108

Bravo AF: 0.0435

Asia WGS AF: 0.0630 AC: 219 AN: 3478

EpiCase AF: 0.0606

EpiControl AF: 0.0626

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Congenital glucose-galactose malabsorption Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	0.48
Dann	Benign	0.76

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: rs33943816; hg19: chr22-32506104; COSMIC: COSV56689723;