dbSNP rs17683448: SLC5A1:p.Ala425Ala (chr22-32091757-C-T) – ACMG Classification: Benign (-19 pts)

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.1275C>T(p.Ala425Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0656 in 1,612,790 control chromosomes in the GnomAD database, including 3,957 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 ( 3746 hom. )

Consequence

SLC5A1
NM_000343.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.111

Publications

10 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet

SLC5A1 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=-0.44).

BP6

Variant 22-32091757-C-T is Benign according to our data. Variant chr22-32091757-C-T is described in ClinVar as Benign. ClinVar VariationId is 341253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.111 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 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.1275C>T	p.Ala425Ala	synonymous	Exon 11 of 15	NP_000334.1	P13866-1
	SLC5A1	NM_001256314.2		c.894C>T	p.Ala298Ala	synonymous	Exon 10 of 14	NP_001243243.1	P13866-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC5A1	ENST00000266088.9	TSL:1 MANE Select	c.1275C>T	p.Ala425Ala	synonymous	Exon 11 of 15	ENSP00000266088.4	P13866-1
SLC5A1	ENST00000878506.1		c.1167C>T	p.Ala389Ala	synonymous	Exon 10 of 14	ENSP00000548565.1
SLC5A1	ENST00000543737.2	TSL:2	c.894C>T	p.Ala298Ala	synonymous	Exon 10 of 14	ENSP00000444898.1	P13866-2

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6839

AN:

151900

Hom.:

212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0413

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.0369

Gnomad FIN

AF:

0.0557

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0706

Gnomad OTH

AF:

0.0369

GnomAD2 exomes

AF:

0.0485

AC:

12176

AN:

250988

AF XY:

0.0495

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:

0.0514

Gnomad NFE exome

AF:

0.0704

Gnomad OTH exome

AF:

0.0455

GnomAD4 exome

AF:

0.0677

AC:

98908

AN:

1460772

Hom.:

3746

Cov.:

AF XY:

0.0669

AC XY:

48648

AN XY:

726762

show subpopulations

African (AFR)

AF:

0.00995

AC:

333

AN:

33468

American (AMR)

AF:

0.0319

AC:

1425

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.0408

AC:

1067

AN:

26130

East Asian (EAS)

AF:

0.00184

AC:

AN:

39690

South Asian (SAS)

AF:

0.0424

AC:

3657

AN:

86236

European-Finnish (FIN)

AF:

0.0564

AC:

3007

AN:

53318

Middle Eastern (MID)

AF:

0.0317

AC:

183

AN:

5764

European-Non Finnish (NFE)

AF:

0.0771

AC:

85663

AN:

1111100

Other (OTH)

AF:

0.0580

AC:

3500

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

4872

9744

14615

19487

24359

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3144

6288

9432

12576

15720

<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:

6840

AN:

152018

Hom.:

211

Cov.:

AF XY:

0.0435

AC XY:

3230

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.0123

AC:

509

AN:

41470

American (AMR)

AF:

0.0347

AC:

529

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0413

AC:

143

AN:

3464

East Asian (EAS)

AF:

0.00116

AC:

AN:

5178

South Asian (SAS)

AF:

0.0374

AC:

179

AN:

4788

European-Finnish (FIN)

AF:

0.0557

AC:

589

AN:

10566

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0706

AC:

4796

AN:

67978

Other (OTH)

AF:

0.0366

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

315

631

946

1262

1577

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:

0.0566

Hom.:

428

Bravo

AF:

0.0428

Asia WGS

AF:

0.0200

AC:

AN:

3478

EpiCase

AF:

0.0604

EpiControl

AF:

0.0660

ClinVar

ClinVar submissions

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

BayesDel_noAF

Benign

-0.44

CADD

Benign

4.5

(source)

DANN

Benign

0.60

PhyloP100

-0.11

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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