Variant 7-103311676-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004279.3(PMPCB):c.1188G>T(p.Glu396Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0852 in 1,613,374 control chromosomes in the GnomAD database, including 6,527 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.065 ( 395 hom., cov: 32)

Exomes 𝑓: 0.087 ( 6132 hom. )

Consequence

PMPCB
NM_004279.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.988

Variant links:

Genes affected

PMPCB (HGNC:9119): (peptidase, mitochondrial processing subunit beta) This gene is a member of the peptidase M16 family and encodes a protein with a zinc-binding motif. This protein is located in the mitochondrial matrix and catalyzes the cleavage of the leader peptides of precursor proteins newly imported into the mitochondria, though it only functions as part of a heterodimeric complex. [provided by RefSeq, Jul 2008]

PMPCB links:

PMPCB (HGNC:):

PMPCB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018229485).

BP6

Variant 7-103311676-G-T is Benign according to our data. Variant chr7-103311676-G-T is described in ClinVar as [Benign]. Clinvar id is 1245557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PMPCB	NM_004279.3 linkuse as main transcript	c.1188G>T	p.Glu396Asp	missense_variant	10/13	ENST00000249269.9	NP_004270.2	O75439Q96CP5B3KM34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PMPCB	ENST00000249269.9 linkuse as main transcript	c.1188G>T	p.Glu396Asp	missense_variant	10/13	1	NM_004279.3	ENSP00000249269.4		O75439

Frequencies

GnomAD3 genomes

AF:

0.0653

AC:

9928

AN:

152146

Hom.:

393

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.0757

Gnomad AMR

AF:

0.0946

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.0506

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.0627

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0808

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0920

AC:

23105

AN:

251110

Hom.:

1381

AF XY:

0.0930

AC XY:

12627

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.0237

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0554

Gnomad EAS exome

AF:

0.0437

Gnomad SAS exome

AF:

0.145

Gnomad FIN exome

AF:

0.0653

Gnomad NFE exome

AF:

0.0801

Gnomad OTH exome

AF:

0.0849

GnomAD4 exome

AF:

0.0873

AC:

127605

AN:

1461110

Hom.:

6132

Cov.:

AF XY:

0.0885

AC XY:

64353

AN XY:

726880

show subpopulations

Gnomad4 AFR exome

AF:

0.0239

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.0569

Gnomad4 EAS exome

AF:

0.0591

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.0660

Gnomad4 NFE exome

AF:

0.0851

Gnomad4 OTH exome

AF:

0.0845

GnomAD4 genome

AF:

0.0652

AC:

9932

AN:

152264

Hom.:

395

Cov.:

AF XY:

0.0658

AC XY:

4898

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0242

Gnomad4 AMR

AF:

0.0945

Gnomad4 ASJ

AF:

0.0631

Gnomad4 EAS

AF:

0.0501

Gnomad4 SAS

AF:

0.130

Gnomad4 FIN

AF:

0.0627

Gnomad4 NFE

AF:

0.0809

Gnomad4 OTH

AF:

0.0601

Alfa

AF:

0.0769

Hom.:

1260

Bravo

AF:

0.0665

TwinsUK

AF:

0.0839

AC:

311

ALSPAC

AF:

0.0820

AC:

316

ESP6500AA

AF:

0.0245

AC:

108

ESP6500EA

AF:

0.0835

AC:

718

ExAC

AF:

0.0906

AC:

11000

Asia WGS

AF:

0.100

AC:

347

AN:

3478

EpiCase

AF:

0.0819

EpiControl

AF:

0.0765

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 19, 2021	- -

PMPCB-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 11, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.14

T;T

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0018

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.16

Sift

Benign

0.29

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.062

B;B

Vest4

0.53

MutPred

0.57

Loss of methylation at R401 (P = 0.1327);Loss of methylation at R401 (P = 0.1327);

MPC

0.18

ClinPred

0.050

GERP RS

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.87

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