11-119024785-C-G

Position:

• chr11-119024785-C-G

Variant summary

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

The NM_001164278.2(SLC37A4):​c.*125G>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 0.276 in 1,195,594 control chromosomes in the GnomAD database, including 47,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (6461 hom., cov: 32)
  • Exomes 𝑓: 0.27 (40626 hom.)
• Consequence: SLC37A4 NM_001164278.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.177

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 (HGNC:):

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-119024785-C-G is Benign according to our data. Variant chr11-119024785-C-G is described in ClinVar as [Benign]. Clinvar id is 302701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A4	NM_001164278.2	c.*125G>C		3_prime_UTR_variant	12/12		NP_001157750.1
SLC37A4	NM_001164277.2	c.*125G>C		3_prime_UTR_variant	11/11		NP_001157749.1
SLC37A4	NM_001164280.2	c.*125G>C		3_prime_UTR_variant	9/9		NP_001157752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775	c.*125G>C		3_prime_UTR_variant	10/10	5		ENSP00000476242.2

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43418 AN: 151996 Hom.: 6451 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.275 AC: 286477 AN: 1043480 Hom.: 40626 Cov.: 14 AF XY: 0.278 AC XY: 146868 AN XY: 527978

Gnomad4 AFR exome AF: 0.323

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.289

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.314

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.282

GnomAD4 genome AF: 0.286 AC: 43473 AN: 152114 Hom.: 6461 Cov.: 32 AF XY: 0.287 AC XY: 21320 AN XY: 74362

Gnomad4 AFR AF: 0.324

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.378

Gnomad4 FIN AF: 0.330

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.289

Alfa AF: 0.272 Hom.: 836

Bravo AF: 0.280

Asia WGS AF: 0.273 AC: 949 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Glycogen storage disease, type I Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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	-0.84
CADD	Benign	3.3
DANN	Benign	0.46
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: rs8301; hg19: chr11-118895495;