rs33954001

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.1845C>G(p.His615Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 1,613,006 control chromosomes in the GnomAD database, including 3,936 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. H615H) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.045 ( 206 hom., cov: 32)

Exomes 𝑓: 0.068 ( 3730 hom. )

Consequence

SLC5A1
NM_000343.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.134

Publications

21 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:

LOC105373000 (HGNC:):

LOC105373000 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=0.0018596649).

BP6

Variant 22-32110063-C-G is Benign according to our data. Variant chr22-32110063-C-G is described in ClinVar as Benign. ClinVar VariationId is 341263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0689 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.1845C>G	p.His615Gln	missense	Exon 15 of 15	NP_000334.1	P13866-1
	SLC5A1	NM_001256314.2		c.1464C>G	p.His488Gln	missense	Exon 14 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.1845C>G	p.His615Gln	missense	Exon 15 of 15	ENSP00000266088.4	P13866-1
SLC5A1	ENST00000878506.1		c.1737C>G	p.His579Gln	missense	Exon 14 of 14	ENSP00000548565.1
SLC5A1	ENST00000543737.2	TSL:2	c.1464C>G	p.His488Gln	missense	Exon 14 of 14	ENSP00000444898.1	P13866-2

Frequencies

GnomAD3 genomes

AF:

0.0450

AC:

6850

AN:

152090

Hom.:

207

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0124

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0344

Gnomad ASJ

AF:

0.0412

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0374

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:

12189

AN:

251408

AF XY:

0.0495

show subpopulations

Gnomad AFR exome

AF:

0.0115

Gnomad AMR exome

AF:

0.0292

Gnomad ASJ exome

AF:

0.0382

Gnomad EAS exome

AF:

0.00125

Gnomad FIN exome

AF:

0.0516

Gnomad NFE exome

AF:

0.0703

Gnomad OTH exome

AF:

0.0451

GnomAD4 exome

AF:

0.0676

AC:

98770

AN:

1460798

Hom.:

3730

Cov.:

AF XY:

0.0668

AC XY:

48572

AN XY:

726754

show subpopulations

African (AFR)

AF:

0.00986

AC:

330

AN:

33468

American (AMR)

AF:

0.0319

AC:

1425

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0408

AC:

1067

AN:

26132

East Asian (EAS)

AF:

0.00184

AC:

AN:

39700

South Asian (SAS)

AF:

0.0423

AC:

3652

AN:

86244

European-Finnish (FIN)

AF:

0.0565

AC:

3020

AN:

53420

Middle Eastern (MID)

AF:

0.0317

AC:

183

AN:

5766

European-Non Finnish (NFE)

AF:

0.0770

AC:

85525

AN:

1110990

Other (OTH)

AF:

0.0579

AC:

3495

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

4612

9224

13836

18448

23060

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3138

6276

9414

12552

15690

<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:

6851

AN:

152208

Hom.:

206

Cov.:

AF XY:

0.0435

AC XY:

3234

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0123

AC:

512

AN:

41508

American (AMR)

AF:

0.0346

AC:

530

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0412

AC:

143

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5188

South Asian (SAS)

AF:

0.0378

AC:

182

AN:

4814

European-Finnish (FIN)

AF:

0.0557

AC:

591

AN:

10606

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0706

AC:

4798

AN:

68008

Other (OTH)

AF:

0.0365

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

330

660

989

1319

1649

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:

0.0538

Hom.:

154

Bravo

AF:

0.0428

TwinsUK

AF:

0.0747

AC:

277

ALSPAC

AF:

0.0810

AC:

312

ESP6500AA

AF:

0.0138

AC:

ESP6500EA

AF:

0.0699

AC:

601

ExAC

AF:

0.0500

AC:

6073

EpiCase

AF:

0.0603

EpiControl

AF:

0.0659

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

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.57

CADD

Benign

6.8

(source)

DANN

Benign

0.28

DEOGEN2

Benign

0.041

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.010

MetaRNN

Benign

0.0019

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-2.0

PhyloP100

0.13

PrimateAI

Benign

0.31

PROVEAN

Benign

1.4

REVEL

Benign

0.21

Sift

Benign

0.65

Sift4G

Benign

0.79

Polyphen

0.0

Vest4

0.012

MutPred

0.41

Gain of loop (P = 0.1081)

MPC

0.47

ClinPred

0.0016

GERP RS

2.9

Varity_R

0.040

gMVP

0.14

Mutation Taster

=98/2

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