rs56394886

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001164277.2(SLC37A4):c.625+14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 1,613,652 control chromosomes in the GnomAD database, including 291 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 42 hom., cov: 33)

Exomes 𝑓: 0.014 ( 249 hom. )

Consequence

SLC37A4
NM_001164277.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0250

Publications

2 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 11-119027614-G-A is Benign according to our data. Variant chr11-119027614-G-A is described in ClinVar as Benign. ClinVar VariationId is 139189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC37A4	NM_001164277.2 link	c.625+14C>T		intron_variant	Intron 6 of 10	ENST00000642844.3	NP_001157749.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9 link	c.625+14C>T		intron_variant	Intron 5 of 9	5		ENSP00000476242.2

Frequencies

GnomAD3 genomes

AF:

0.0133

AC:

2020

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00425

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00693

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.0520

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.0179

AC:

4455

AN:

248812

AF XY:

0.0179

show subpopulations

Gnomad AFR exome

AF:

0.00465

Gnomad AMR exome

AF:

0.00898

Gnomad ASJ exome

AF:

0.00358

Gnomad EAS exome

AF:

0.0625

Gnomad FIN exome

AF:

0.0468

Gnomad NFE exome

AF:

0.0115

Gnomad OTH exome

AF:

0.0126

GnomAD4 exome

AF:

0.0139

AC:

20356

AN:

1461326

Hom.:

249

Cov.:

AF XY:

0.0140

AC XY:

10179

AN XY:

726970

show subpopulations

African (AFR)

AF:

0.00392

AC:

131

AN:

33450

American (AMR)

AF:

0.00883

AC:

395

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00249

AC:

AN:

26136

East Asian (EAS)

AF:

0.0411

AC:

1630

AN:

39688

South Asian (SAS)

AF:

0.0179

AC:

1536

AN:

85986

European-Finnish (FIN)

AF:

0.0443

AC:

2367

AN:

53382

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0121

AC:

13441

AN:

1111836

Other (OTH)

AF:

0.0128

AC:

771

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1107

2214

3322

4429

5536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.0133

AC:

2022

AN:

152326

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1176

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00426

AC:

177

AN:

41562

American (AMR)

AF:

0.00686

AC:

105

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0569

AC:

295

AN:

5182

South Asian (SAS)

AF:

0.0182

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0520

AC:

552

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

776

AN:

68030

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

199

298

398

497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00919

Hom.:

Bravo

AF:

0.0107

Asia WGS

AF:

0.0220

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jul 11, 2018

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 25, 2013

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. -

Glucose-6-phosphate transport defect

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Phosphate transport defect

Benign:1

Jul 01, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.88

(source)

DANN

Benign

0.67

PhyloP100

-0.025

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over