Genetic Variant ENST00000330775.9:c.174A>T (chr11-119028401-T-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The ENST00000330775.9(SLC37A4):c.174A>T(p.Ala58Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,312 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A58A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SLC37A4
ENST00000330775.9 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0600

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	Protein	UniProt
SLC37A4	NM_001164279.2 link	c.-46A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 4 of 11	NP_001157751.1	O43826B4DUH2
SLC37A4	NM_001164278.2 link	c.174A>T	p.Ala58Ala	synonymous_variant	Exon 4 of 12	NP_001157750.1	O43826-2A0A024R3L1
SLC37A4	NM_001164277.2 link	c.174A>T	p.Ala58Ala	synonymous_variant	Exon 4 of 11	NP_001157749.1	O43826-1A0A024R3H9A8K0S7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9 link	c.174A>T	p.Ala58Ala	synonymous_variant	Exon 3 of 10	5		ENSP00000476242.2		U3KPU7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1441312

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

714980

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33020

American (AMR)

AF:

0.00

AC:

AN:

41282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25650

East Asian (EAS)

AF:

0.00

AC:

AN:

38724

South Asian (SAS)

AF:

0.0000241

AC:

AN:

82932

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52154

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102086

Other (OTH)

AF:

0.00

AC:

AN:

59718

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.5

(source)

DANN

Benign

0.82

PhyloP100

0.060

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over