rs79849261

chr11-119028440-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001164279.2(SLC37A4):c.-71-14A>G variant causes a splice polypyrimidine tract, 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_001164279.2 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.06

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 -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 [Likely_benign]. Clinvar id is 139186.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119028440-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC37A4	NM_001164277.2	c.149-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000642844.3
SLC37A4	NM_001164279.2	c.-71-14A>G		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC37A4	ENST00000330775.9	c.149-14A>G		splice_polypyrimidine_tract_variant, intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0127 AC: 1938 AN: 152086 Hom.: 43 Cov.: 33

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

GnomAD3 exomes AF: 0.0179 AC: 3041 AN: 170162 Hom.: 64 AF XY: 0.0180 AC XY: 1630 AN XY: 90392

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 SAS exome AF: 0.0183

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.: 27 AF XY: 0.0139 AC XY: 9624 AN XY: 690570

Gnomad4 AFR exome AF: 0.00195

Gnomad4 AMR exome AF: 0.00865

Gnomad4 ASJ exome AF: 0.00232

Gnomad4 EAS exome AF: 0.0390

Gnomad4 SAS exome AF: 0.0182

Gnomad4 FIN exome AF: 0.0448

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0126

GnomAD4 genome AF: 0.0127 AC: 1939 AN: 152204 Hom.: 42 Cov.: 33 AF XY: 0.0151 AC XY: 1127 AN XY: 74402

Gnomad4 AFR AF: 0.00250

Gnomad4 AMR AF: 0.00628

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0560

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0528

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00887 Hom.: 3

Bravo AF: 0.0101

Asia WGS AF: 0.0230 AC: 78 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2013	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Glucose-6-phosphate transport defect Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Glycogen storage disease, type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

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

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jul 21, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Aug 21, 2023

- -

Phosphate transport defect Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
Cadd	Benign	9.6
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs79849261; hg19: chr11-118899150;