rs34871377

Positions:

• chr11-119024922-C-T

Variant summary

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

The NM_001164278.2(SLC37A4):​c.1344G>A​(p.Lys448Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00298 in 1,613,788 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (75 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (89 hom.)
• Consequence: SLC37A4 NM_001164278.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 3.52

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027157962).
• BP6: Variant 11-119024922-C-T is Benign according to our data. Variant chr11-119024922-C-T is described in ClinVar as [Benign]. Clinvar id is 139194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-119024922-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=3.52 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A4	NM_001164278.2	c.1344G>A	p.Lys448Lys	synonymous_variant	12/12		NP_001157750.1
SLC37A4	NM_001164277.2	c.1278G>A	p.Lys426Lys	synonymous_variant	11/11		NP_001157749.1
SLC37A4	NM_001164280.2	c.1278G>A	p.Lys426Lys	synonymous_variant	9/9		NP_001157752.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9	c.1278G>A	p.Lys426Lys	synonymous_variant	10/10	5		ENSP00000476242.2

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2372 AN: 152246 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0550

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.0100

GnomAD3 exomes AF: 0.00399 AC: 991 AN: 248538 Hom.: 37 AF XY: 0.00303 AC XY: 409 AN XY: 134860

Gnomad AFR exome AF: 0.0582

Gnomad AMR exome AF: 0.00226

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000983

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000710

Gnomad OTH exome AF: 0.000830

GnomAD4 exome AF: 0.00165 AC: 2418 AN: 1461424 Hom.: 89 Cov.: 32 AF XY: 0.00148 AC XY: 1077 AN XY: 726954

Gnomad4 AFR exome AF: 0.0593

Gnomad4 AMR exome AF: 0.00231

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000337

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.00408

GnomAD4 genome AF: 0.0157 AC: 2385 AN: 152364 Hom.: 75 Cov.: 33 AF XY: 0.0157 AC XY: 1169 AN XY: 74512

Gnomad4 AFR AF: 0.0551

Gnomad4 AMR AF: 0.00385

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.00353 Hom.: 15

Bravo AF: 0.0178

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0540 AC: 218

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00499 AC: 604

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 23, 2014	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, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	12
DANN	Benign	0.89
Eigen	Benign	0.028
Eigen_PC	Benign	0.064
FATHMM_MKL	Uncertain	0.96	D
MetaRNN	Benign	0.0027	T
MetaSVM	Benign	-0.86	T
PROVEAN	Benign	-0.71	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Vest4		0.45
MVP		0.65
ClinPred		0.054	T
GERP RS		4.4

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: rs34871377; hg19: chr11-118895632;