Variant 21-42535534-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001320537.2(SLC37A1):c.334G>A(p.Val112Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 1 hom. )

Consequence

SLC37A1
NM_001320537.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.624

Variant links:

Genes affected

SLC37A1 (HGNC:11024): (solute carrier family 37 member 1) The protein encoded by this gene localizes to the endoplasmic reticulum (ER) membrane. This protein translocates glucose-6-phosphate from the cytoplasm into the lumen of the ER for hydrolysis into glucose by another ER membrane protein. This gene is a member of the solute carrier 37 gene family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

SLC37A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033257574).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC37A1	NM_001320537.2 linkuse as main transcript	c.334G>A	p.Val112Met	missense_variant	5/20	ENST00000352133.3	NP_001307466.1	P57057

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC37A1	ENST00000352133.3 linkuse as main transcript	c.334G>A	p.Val112Met	missense_variant	5/20	1	NM_001320537.2	ENSP00000344648.2		P57057
SLC37A1	ENST00000398341.7 linkuse as main transcript	c.334G>A	p.Val112Met	missense_variant	6/21	1		ENSP00000381383.3		P57057

Frequencies

GnomAD3 genomes

AF:

0.000545

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000274

AC:

AN:

251458

Hom.:

AF XY:

0.000250

AC XY:

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000125

AC:

182

AN:

1461800

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00152

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000591

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000215

GnomAD4 genome

AF:

0.000545

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000497

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00159

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000161

Hom.:

Bravo

AF:

0.000548

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000264

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 22, 2024

The c.334G>A (p.V112M) alteration is located in exon 6 (coding exon 4) of the SLC37A1 gene. This alteration results from a G to A substitution at nucleotide position 334, causing the valine (V) at amino acid position 112 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;T

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.080

LIST_S2

Uncertain

0.97

.;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.033

T;T

MetaSVM

Benign

-0.75

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.17

Sift

Uncertain

0.020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.67

P;P

Vest4

0.47

MVP

0.35

MPC

0.89

ClinPred

0.065

GERP RS

-3.9

Varity_R

0.072

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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