Variant 21-42534740-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001320537.2(SLC37A1):c.181G>A(p.Val61Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,613,916 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 53 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 45 hom. )

Consequence

SLC37A1
NM_001320537.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.916

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031147301).

BP6

Variant 21-42534740-G-A is Benign according to our data. Variant chr21-42534740-G-A is described in ClinVar as [Benign]. Clinvar id is 784885.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0147 (2237/152214) while in subpopulation AFR AF= 0.0505 (2098/41514). AF 95% confidence interval is 0.0487. There are 53 homozygotes in gnomad4. There are 1061 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 53 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC37A1	NM_001320537.2 linkuse as main transcript	c.181G>A	p.Val61Ile	missense_variant	4/20	ENST00000352133.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC37A1	ENST00000352133.3 linkuse as main transcript	c.181G>A	p.Val61Ile	missense_variant	4/20	1	NM_001320537.2	P1
SLC37A1	ENST00000398341.7 linkuse as main transcript	c.181G>A	p.Val61Ile	missense_variant	5/21	1		P1

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2233

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0143

GnomAD3 exomes

AF:

0.00395

AC:

993

AN:

251304

Hom.:

AF XY:

0.00289

AC XY:

392

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.0523

Gnomad AMR exome

AF:

0.00313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00153

AC:

2235

AN:

1461702

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

943

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0511

Gnomad4 AMR exome

AF:

0.00342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.00310

GnomAD4 genome

AF:

0.0147

AC:

2237

AN:

152214

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1061

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0505

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0142

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.0170

ESP6500AA

AF:

0.0488

AC:

215

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00479

AC:

581

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.78

CADD

Benign

6.4

DANN

Benign

0.69

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.22

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.98

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.038

Sift

Benign

0.74

T;T

Sift4G

Benign

0.85

T;T

Polyphen

0.0090

B;B

Vest4

0.12

MVP

0.26

MPC

0.32

ClinPred

0.00026

GERP RS

1.4

Varity_R

0.019

gMVP

0.17

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