Variant chr4-7061167-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_025196.4(GRPEL1):c.349G>A(p.Val117Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000637 in 1,613,556 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00046 ( 1 hom. )

Consequence

GRPEL1
NM_025196.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.14

Variant links:

Genes affected

GRPEL1 (HGNC:19696): (GrpE like 1, mitochondrial) Enables identical protein binding activity and unfolded protein binding activity. Predicted to be involved in protein import into mitochondrial matrix. Located in mitochondrial matrix and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

GRPEL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011043102).

BP6

Variant 4-7061167-C-T is Benign according to our data. Variant chr4-7061167-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654632.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GRPEL1	NM_025196.4 linkuse as main transcript	c.349G>A	p.Val117Ile	missense_variant	4/4	ENST00000264954.5	NP_079472.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GRPEL1	ENST00000264954.5 linkuse as main transcript	c.349G>A	p.Val117Ile	missense_variant	4/4	1	NM_025196.4	ENSP00000264954	P1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00770

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000929

AC:

233

AN:

250746

Hom.:

AF XY:

0.000804

AC XY:

109

AN XY:

135520

show subpopulations

Gnomad AFR exome

AF:

0.00837

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00549

Gnomad EAS exome

AF:

0.000870

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000970

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000455

AC:

665

AN:

1461252

Hom.:

Cov.:

AF XY:

0.000436

AC XY:

317

AN XY:

726944

show subpopulations

Gnomad4 AFR exome

AF:

0.00928

Gnomad4 AMR exome

AF:

0.000515

Gnomad4 ASJ exome

AF:

0.00521

Gnomad4 EAS exome

AF:

0.000781

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000792

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.00238

AC:

363

AN:

152304

Hom.:

Cov.:

AF XY:

0.00235

AC XY:

175

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00792

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000779

Hom.:

Bravo

AF:

0.00280

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000972

AC:

118

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

GRPEL1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.0090

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.71

M_CAP

Benign

0.0022

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.78

MutationTaster

Benign

0.85

PrimateAI

Benign

0.31

PROVEAN

Benign

0.40

REVEL

Benign

0.19

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.047

MVP

0.12

MPC

0.18

ClinPred

0.00038

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.021

gMVP

0.18

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