11-119024492-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001164279.2(SLC37A4):c.*418T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 249,338 control chromosomes in the GnomAD database, including 5,119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (3024 hom., cov: 32)
  • Exomes 𝑓: 0.19 (2095 hom.)
• Consequence: SLC37A4 NM_001164279.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.290

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]

TRAPPC4 (HGNC:19943): (trafficking protein particle complex subunit 4) Involved in autophagy and endoplasmic reticulum to Golgi vesicle-mediated transport. Part of TRAPP complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 11-119024492-A-G is Benign according to our data. Variant chr11-119024492-A-G is described in ClinVar as [Benign]. Clinvar id is 302695.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.311 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC37A4	NM_001164277.2	c.*418T>C		3_prime_UTR_variant	11/11	ENST00000642844.3
SLC37A4	NM_001164279.2	c.*418T>C		3_prime_UTR_variant	11/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC37A4	ENST00000330775.9	c.*418T>C		3_prime_UTR_variant	10/10	5		P1

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28977 AN: 151974 Hom.: 3021 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0911

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.191 AC: 18618 AN: 97246 Hom.: 2095 Cov.: 0 AF XY: 0.200 AC XY: 10184 AN XY: 50992

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.164

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.0879

Gnomad4 SAS exome AF: 0.264

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.185

GnomAD4 genome AF: 0.191 AC: 28992 AN: 152092 Hom.: 3024 Cov.: 32 AF XY: 0.192 AC XY: 14261 AN XY: 74348

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.0913

Gnomad4 SAS AF: 0.325

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.205

Alfa AF: 0.214 Hom.: 3966

Bravo AF: 0.180

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.9
Dann	Benign	0.53
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

LitVar

Other links and lift over

dbSNP: rs11006; hg19: chr11-118895202;