rs34123220

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000330775.9(SLC37A4):c.183T>C(p.Ala61Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00827 in 1,598,914 control chromosomes in the GnomAD database, including 831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.041 ( 413 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 418 hom. )

Consequence

SLC37A4
ENST00000330775.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.72

Publications

4 publications found

Variant links:

Genes affected

SLC37A4 (HGNC:4061): (solute carrier family 37 member 4) This gene regulates glucose-6-phosphate transport from the cytoplasm to the lumen of the endoplasmic reticulum, in order to maintain glucose homeostasis. It also plays a role in ATP-mediated calcium sequestration in the lumen of the endoplasmic reticulum. Mutations in this gene have been associated with various forms of glycogen storage disease. Alternative splicing in this gene results in multiple transcript variants.[provided by RefSeq, Aug 2009]

SLC37A4 Gene-Disease associations (from GenCC):

congenital disorder of glycosylation, type IIw
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
glycogen storage disease Ib
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
glycogen storage disease type 1 due to SLC37A4 mutation
Inheritance: AR Classification: DEFINITIVE Submitted by: Myriad Women’s Health

SLC37A4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 11-119028392-A-G is Benign according to our data. Variant chr11-119028392-A-G is described in ClinVar as Benign. ClinVar VariationId is 139187.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.72 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
SLC37A4	NM_001164278.2 link	c.183T>C	p.Ala61Ala	synonymous_variant	Exon 4 of 12	NP_001157750.1	O43826-2A0A024R3L1
SLC37A4	NM_001164277.2 link	c.183T>C	p.Ala61Ala	synonymous_variant	Exon 4 of 11	NP_001157749.1	O43826-1A0A024R3H9A8K0S7
SLC37A4	NM_001164280.2 link	c.183T>C	p.Ala61Ala	synonymous_variant	Exon 2 of 9	NP_001157752.1	O43826-1A0A024R3H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9 link	c.183T>C	p.Ala61Ala	synonymous_variant	Exon 3 of 10	5		ENSP00000476242.2		U3KPU7

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6290

AN:

152158

Hom.:

409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0256

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00109

Gnomad OTH

AF:

0.0315

GnomAD2 exomes

AF:

0.0111

AC:

2470

AN:

222984

AF XY:

0.00827

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.000210

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000597

Gnomad NFE exome

AF:

0.000983

Gnomad OTH exome

AF:

0.00816

GnomAD4 exome

AF:

0.00477

AC:

6902

AN:

1446638

Hom.:

418

Cov.:

AF XY:

0.00417

AC XY:

2997

AN XY:

718106

show subpopulations

African (AFR)

AF:

0.141

AC:

4672

AN:

33116

American (AMR)

AF:

0.0126

AC:

532

AN:

42192

Ashkenazi Jewish (ASJ)

AF:

0.000349

AC:

AN:

25766

East Asian (EAS)

AF:

0.00

AC:

AN:

39054

South Asian (SAS)

AF:

0.000227

AC:

AN:

83662

European-Finnish (FIN)

AF:

0.000648

AC:

AN:

52492

Middle Eastern (MID)

AF:

0.0130

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000778

AC:

859

AN:

1104706

Other (OTH)

AF:

0.0117

AC:

702

AN:

59898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

333

665

998

1330

1663

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.0415

AC:

6316

AN:

152276

Hom.:

413

Cov.:

AF XY:

0.0398

AC XY:

2962

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.139

AC:

5775

AN:

41510

American (AMR)

AF:

0.0256

AC:

392

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

68026

Other (OTH)

AF:

0.0312

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

278

556

835

1113

1391

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0217

Hom.:

170

Bravo

AF:

0.0485

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 22, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Glucose-6-phosphate transport defect

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Glycogen storage disease, type I

Benign:1

Jan 12, 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 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

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.57

PhyloP100

1.7

Mutation Taster

=280/20

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over