rs17683430

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_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. 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

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.30

Publications

35 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC5A1	NM_000343.4	MANE Select	c.1231G>A	p.Ala411Thr	missense	Exon 11 of 15	NP_000334.1
	SLC5A1	NM_001256314.2		c.850G>A	p.Ala284Thr	missense	Exon 10 of 14	NP_001243243.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC5A1	ENST00000266088.9	TSL:1 MANE Select	c.1231G>A	p.Ala411Thr	missense	Exon 11 of 15	ENSP00000266088.4
SLC5A1	ENST00000878506.1		c.1123G>A	p.Ala375Thr	missense	Exon 10 of 14	ENSP00000548565.1
SLC5A1	ENST00000543737.2	TSL:2	c.850G>A	p.Ala284Thr	missense	Exon 10 of 14	ENSP00000444898.1

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

GnomAD2 exomes

AF:

0.0486

AC:

12204

AN:

251274

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:

0.00131

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.:

AF XY:

0.0670

AC XY:

48693

AN XY:

727002

show subpopulations

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:

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

5029

10058

15086

20115

25144

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3150

6300

9450

12600

15750

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0450

AC:

6841

AN:

152068

Hom.:

207

Cov.:

AF XY:

0.0435

AC XY:

3229

AN XY:

74310

show subpopulations

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:

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.0705

AC:

4794

AN:

67988

Other (OTH)

AF:

0.0365

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

312

624

937

1249

1561

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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:

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital glucose-galactose malabsorption (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.21

DEOGEN2

Benign

0.047

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.38

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.46

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.1

PhyloP100

4.3

PrimateAI

Uncertain

0.61

PROVEAN

Benign

2.2

REVEL

Benign

0.28

Sift

Benign

0.97

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.046

MPC

0.45

ClinPred

0.0080

GERP RS

5.9

Varity_R

0.097

gMVP

0.30

Mutation Taster

=94/6

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over