rs8192696

Positions:

chr11-119024976-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001164278.2(SLC37A4):c.1290G>A(p.Thr430Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 1,613,786 control chromosomes in the GnomAD database, including 42,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5112 hom., cov: 33)

Exomes 𝑓: 0.22 ( 37150 hom. )

Consequence

SLC37A4
NM_001164278.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -1.13

Variant links:

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 links:

SLC37A4 (HGNC:):

SLC37A4 links:

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]

TRAPPC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0030011535).

BP6

Variant 11-119024976-C-T is Benign according to our data. Variant chr11-119024976-C-T is described in ClinVar as [Benign]. Clinvar id is 139192.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.13 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
SLC37A4	NM_001164278.2 linkuse as main transcript	c.1290G>A	p.Thr430Thr	synonymous_variant	12/12	NP_001157750.1	O43826-2A0A024R3L1
SLC37A4	NM_001164277.2 linkuse as main transcript	c.1224G>A	p.Thr408Thr	synonymous_variant	11/11	NP_001157749.1	O43826-1A0A024R3H9A8K0S7
SLC37A4	NM_001164280.2 linkuse as main transcript	c.1224G>A	p.Thr408Thr	synonymous_variant	9/9	NP_001157752.1	O43826-1A0A024R3H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A4	ENST00000330775.9 linkuse as main transcript	c.1224G>A	p.Thr408Thr	synonymous_variant	10/10	5		ENSP00000476242.2		U3KPU7

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37675

AN:

152096

Hom.:

5085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.347

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.210

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.0891

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.212

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.214

AC:

53158

AN:

248950

Hom.:

6371

AF XY:

0.220

AC XY:

29688

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.149

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.0901

Gnomad SAS exome

AF:

0.294

Gnomad FIN exome

AF:

0.225

Gnomad NFE exome

AF:

0.211

Gnomad OTH exome

AF:

0.219

GnomAD4 exome

AF:

0.222

AC:

324203

AN:

1461572

Hom.:

37150

Cov.:

AF XY:

0.224

AC XY:

162849

AN XY:

727054

show subpopulations

Gnomad4 AFR exome

AF:

0.355

Gnomad4 AMR exome

AF:

0.158

Gnomad4 ASJ exome

AF:

0.189

Gnomad4 EAS exome

AF:

0.114

Gnomad4 SAS exome

AF:

0.292

Gnomad4 FIN exome

AF:

0.221

Gnomad4 NFE exome

AF:

0.219

Gnomad4 OTH exome

AF:

0.232

GnomAD4 genome

AF:

0.248

AC:

37746

AN:

152214

Hom.:

5112

Cov.:

AF XY:

0.248

AC XY:

18424

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.0893

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.212

Gnomad4 OTH

AF:

0.249

Alfa

AF:

0.222

Hom.:

3352

Bravo

AF:

0.247

TwinsUK

AF:

0.216

AC:

800

ALSPAC

AF:

0.216

AC:

834

ESP6500AA

AF:

0.337

AC:

1363

ESP6500EA

AF:

0.216

AC:

1809

ExAC

AF:

0.218

AC:

26367

Asia WGS

AF:

0.233

AC:

813

AN:

3478

EpiCase

AF:

0.212

EpiControl

AF:

0.220

ClinVar

Significance: Benign

Submissions summary: Benign:7Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Glucose-6-phosphate transport defect

Benign:3

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 01, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 29, 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. -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

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_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.33

CADD

Benign

8.6

DANN

Benign

0.85

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.14

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.98

PROVEAN

Benign

0.040

REVEL

Benign

0.10

Sift

Pathogenic

0.0

Vest4

0.093

ClinPred

0.016

GERP RS

-0.051

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over