ENST00000330775.9:c.183T>C

Variant names:

• chr11-119028392-A-G
• rs34123220
• ENST00000330775.9:c.183T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.72

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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	MANE	Protein	UniProt
SLC37A4	NM_001164278.2	c.183T>C	p.Ala61Ala	synonymous_variant	Exon 4 of 12		NP_001157750.1
SLC37A4	NM_001164277.2	c.183T>C	p.Ala61Ala	synonymous_variant	Exon 4 of 11		NP_001157749.1
SLC37A4	NM_001164280.2	c.183T>C	p.Ala61Ala	synonymous_variant	Exon 2 of 9		NP_001157752.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0413 AC: 6290 AN: 152158 Hom.: 409 Cov.: 33

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

GnomAD3 exomes AF: 0.0111 AC: 2470 AN: 222984 Hom.: 163 AF XY: 0.00827 AC XY: 996 AN XY: 120400

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 SAS exome AF: 0.000219

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.: 32 AF XY: 0.00417 AC XY: 2997 AN XY: 718106

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.0126

Gnomad4 ASJ exome AF: 0.000349

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000227

Gnomad4 FIN exome AF: 0.000648

Gnomad4 NFE exome AF: 0.000778

Gnomad4 OTH exome AF: 0.0117

GnomAD4 genome AF: 0.0415 AC: 6316 AN: 152276 Hom.: 413 Cov.: 33 AF XY: 0.0398 AC XY: 2962 AN XY: 74460

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000377

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0236 Hom.: 123

Bravo AF: 0.0485

Asia WGS AF: 0.00606 AC: 21 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

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	12
DANN	Benign	0.57

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

LitVar

Other links and lift over

dbSNP: rs34123220; hg19: chr11-118899102;