rs79849261

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.149-14A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0137 in 1,547,762 control chromosomes in the GnomAD database, including 275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 42 hom., cov: 33)

Exomes 𝑓: 0.014 ( 233 hom. )

Consequence

SLC37A4
NM_001164277.2 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 1.06

Publications

3 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
glycogen storage disease Ib
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Genomics England PanelApp, 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=-0.65).

BP6

Variant 11-119028440-T-C is Benign according to our data. Variant chr11-119028440-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 139186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164277.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC37A4	NM_001164277.2	MANE Select	c.149-14A>G	intron	N/A	NP_001157749.1	O43826-1
SLC37A4	NM_001164278.2		c.149-14A>G	intron	N/A	NP_001157750.1	O43826-2
SLC37A4	NM_001164280.2		c.149-14A>G	intron	N/A	NP_001157752.1	O43826-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC37A4	ENST00000330775.9	TSL:5	c.149-14A>G	intron	N/A	ENSP00000476242.2	U3KPU7
SLC37A4	ENST00000526275.5	TSL:1	n.595A>G	non_coding_transcript_exon	Exon 1 of 6
SLC37A4	ENST00000532085.1	TSL:1	n.2424A>G	non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes

AF:

0.0127

AC:

1938

AN:

152086

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00642

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.0557

Gnomad SAS

AF:

0.0182

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0114

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.0179

AC:

3041

AN:

170162

AF XY:

0.0180

show subpopulations

Gnomad AFR exome

AF:

0.00239

Gnomad AMR exome

AF:

0.00905

Gnomad ASJ exome

AF:

0.00341

Gnomad EAS exome

AF:

0.0612

Gnomad FIN exome

AF:

0.0472

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.0138

AC:

19307

AN:

1395558

Hom.:

233

Cov.:

AF XY:

0.0139

AC XY:

9624

AN XY:

690570

show subpopulations

African (AFR)

AF:

0.00195

AC:

AN:

31788

American (AMR)

AF:

0.00865

AC:

318

AN:

36778

Ashkenazi Jewish (ASJ)

AF:

0.00232

AC:

AN:

24996

East Asian (EAS)

AF:

0.0390

AC:

1434

AN:

36766

South Asian (SAS)

AF:

0.0182

AC:

1455

AN:

79876

European-Finnish (FIN)

AF:

0.0448

AC:

2197

AN:

49014

Middle Eastern (MID)

AF:

0.00353

AC:

AN:

5668

European-Non Finnish (NFE)

AF:

0.0122

AC:

13033

AN:

1072576

Other (OTH)

AF:

0.0126

AC:

730

AN:

58096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

966

1931

2897

3862

4828

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.0127

AC:

1939

AN:

152204

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1127

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.00250

AC:

104

AN:

41522

American (AMR)

AF:

0.00628

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.0560

AC:

290

AN:

5174

South Asian (SAS)

AF:

0.0184

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0528

AC:

560

AN:

10600

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0114

AC:

773

AN:

68004

Other (OTH)

AF:

0.00758

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

189

283

378

472

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00887

Hom.:

Bravo

AF:

0.0101

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glucose-6-phosphate transport defect (2)

not provided (2)

not specified (2)

Glucose-6-phosphate transport defect;C0342749:Phosphate transport defect;C5561986:Congenital disorder of glycosylation, type IIw (1)

Glycogen storage disease, type I (1)

Phosphate transport defect (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

9.6

(source)

DANN

Benign

0.51

PhyloP100

1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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