rs56394886

chr11-119027614-G-A

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.406+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_001164279.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0250

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=-0.84).
• BP6: Variant 11-119027614-G-A is Benign according to our data. Variant chr11-119027614-G-A is described in ClinVar as [Benign]. Clinvar id is 139189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119027614-G-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
SLC37A4	NM_001164277.2	c.625+14C>T		intron_variant		ENST00000642844.3
SLC37A4	NM_001164279.2	c.406+14C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC37A4	ENST00000330775.9	c.625+14C>T		intron_variant		5		P1

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 2020 AN: 152208 Hom.: 42 Cov.: 33

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

GnomAD3 exomes AF: 0.0179 AC: 4455 AN: 248812 Hom.: 92 AF XY: 0.0179 AC XY: 2416 AN XY: 135034

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 SAS exome AF: 0.0175

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.: 32 AF XY: 0.0140 AC XY: 10179 AN XY: 726970

Gnomad4 AFR exome AF: 0.00392

Gnomad4 AMR exome AF: 0.00883

Gnomad4 ASJ exome AF: 0.00249

Gnomad4 EAS exome AF: 0.0411

Gnomad4 SAS exome AF: 0.0179

Gnomad4 FIN exome AF: 0.0443

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.0128

GnomAD4 genome AF: 0.0133 AC: 2022 AN: 152326 Hom.: 42 Cov.: 33 AF XY: 0.0158 AC XY: 1176 AN XY: 74492

Gnomad4 AFR AF: 0.00426

Gnomad4 AMR AF: 0.00686

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.0569

Gnomad4 SAS AF: 0.0182

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0114

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00919 Hom.: 3

Bravo AF: 0.0107

Asia WGS AF: 0.0220 AC: 75 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	Eurofins Ntd Llc (ga)	Jul 11, 2018	- -

Glucose-6-phosphate transport defect Benign:2

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

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	-0.84
Cadd	Benign	0.88
Dann	Benign	0.67

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: rs56394886; hg19: chr11-118898324;