rs17683430

Variant names:

• chr22-32091713-G-A
• rs17683430
• NM_000343.4:c.1231G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-32091713-G-A
• chr22-32091713-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A411V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.045 (207 hom., cov: 32)
  • Exomes 𝑓: 0.068 (3738 hom.)
• Consequence: SLC5A1 NM_000343.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.30
• Publications: 35 publications found

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)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• 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 VariationId 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 rank	MANE	Protein	UniProt
SLC5A1	NM_000343.4	c.1231G>A	p.Ala411Thr	missense_variant	Exon 11 of 15	ENST00000266088.9	NP_000334.1
SLC5A1	NM_001256314.2	c.850G>A	p.Ala284Thr	missense_variant	Exon 10 of 14		NP_001243243.1
SLC5A1	XM_011530331.2	c.1231G>A	p.Ala411Thr	missense_variant	Exon 11 of 12		XP_011528633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A1	ENST00000266088.9	c.1231G>A	p.Ala411Thr	missense_variant	Exon 11 of 15	1	NM_000343.4	ENSP00000266088.4
SLC5A1	ENST00000543737.2	c.850G>A	p.Ala284Thr	missense_variant	Exon 10 of 14	2		ENSP00000444898.1
SLC5A1	ENST00000477969.1	n.397G>A		non_coding_transcript_exon_variant	Exon 3 of 5	3

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6840 AN: 151950 Hom.: 208 Cov.: 32

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

GnomAD2 exomes AF: 0.0486 AC: 12204 AN: 251274 AF XY: 0.0496

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 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.: 31 AF XY: 0.0670 AC XY: 48693 AN XY: 727002

African (AFR) AF: 0.00995 AC: 333 AN: 33480

American (AMR) AF: 0.0318 AC: 1421 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0408 AC: 1066 AN: 26132

East Asian (EAS) AF: 0.00186 AC: 74 AN: 39700

South Asian (SAS) AF: 0.0425 AC: 3663 AN: 86252

European-Finnish (FIN) AF: 0.0565 AC: 3019 AN: 53410

Middle Eastern (MID) AF: 0.0317 AC: 183 AN: 5766

European-Non Finnish (NFE) AF: 0.0772 AC: 85755 AN: 1111500

Other (OTH) AF: 0.0581 AC: 3508 AN: 60384

GnomAD4 genome AF: 0.0450 AC: 6841 AN: 152068 Hom.: 207 Cov.: 32 AF XY: 0.0435 AC XY: 3229 AN XY: 74310

African (AFR) AF: 0.0123 AC: 512 AN: 41496

American (AMR) AF: 0.0344 AC: 525 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0412 AC: 143 AN: 3468

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5166

South Asian (SAS) AF: 0.0379 AC: 182 AN: 4808

European-Finnish (FIN) AF: 0.0559 AC: 590 AN: 10556

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0705 AC: 4794 AN: 67988

Other (OTH) AF: 0.0365 AC: 77 AN: 2108

Alfa AF: 0.0577 Hom.: 682

Bravo AF: 0.0427

TwinsUK AF: 0.0747 AC: 277

ALSPAC AF: 0.0791 AC: 305

ESP6500AA AF: 0.0138 AC: 61

ESP6500EA AF: 0.0700 AC: 602

ExAC AF: 0.0501 AC: 6079

Asia WGS AF: 0.0200 AC: 70 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

- -

Mar 06, 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
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	16
DANN	Benign	0.21
DEOGEN2	Benign	0.047	T;.
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.33	N
LIST_S2	Benign	0.46	T;T
MetaRNN	Benign	0.0034	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.1	N;.
PhyloP100		4.3
PrimateAI	Uncertain	0.61	T
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	T
GERP RS		5.9
Varity_R		0.097
gMVP		0.30
Mutation Taster		=94/6	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17683430; hg19: chr22-32487700; COSMIC: COSV56682960;