Genetic Variant NM_004279.3:c.104T>C (chr7-103298572-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_004279.3(PMPCB):c.104T>C(p.Leu35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 1,613,538 control chromosomes in the GnomAD database, including 2,697 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 Benign (★★).

Frequency

Genomes: 𝑓 0.075 ( 1439 hom., cov: 33)

Exomes 𝑓: 0.0079 ( 1258 hom. )

Consequence

PMPCB
NM_004279.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0510

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:

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=0.0033938587).

BP6

Variant 7-103298572-T-C is Benign according to our data. Variant chr7-103298572-T-C is described in ClinVar as [Benign]. Clinvar id is 1268549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMPCB	NM_004279.3 link	c.104T>C	p.Leu35Ser	missense_variant	Exon 2 of 13	ENST00000249269.9	NP_004270.2	O75439Q96CP5B3KM34

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMPCB	ENST00000249269.9 link	c.104T>C	p.Leu35Ser	missense_variant	Exon 2 of 13	1	NM_004279.3	ENSP00000249269.4		O75439

Frequencies

GnomAD3 genomes

AF:

0.0754

AC:

11467

AN:

152102

Hom.:

1436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0258

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00112

Gnomad OTH

AF:

0.0602

GnomAD3 exomes

AF:

0.0200

AC:

5016

AN:

251238

Hom.:

590

AF XY:

0.0144

AC XY:

1951

AN XY:

135788

show subpopulations

Gnomad AFR exome

AF:

0.267

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000809

Gnomad OTH exome

AF:

0.0116

GnomAD4 exome

AF:

0.00788

AC:

11517

AN:

1461318

Hom.:

1258

Cov.:

AF XY:

0.00680

AC XY:

4946

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.270

Gnomad4 AMR exome

AF:

0.0167

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000522

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000517

Gnomad4 OTH exome

AF:

0.0173

GnomAD4 genome

AF:

0.0755

AC:

11490

AN:

152220

Hom.:

1439

Cov.:

AF XY:

0.0724

AC XY:

5392

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.263

Gnomad4 AMR

AF:

0.0257

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00112

Gnomad4 OTH

AF:

0.0596

Alfa

AF:

0.0324

Hom.:

328

Bravo

AF:

0.0859

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.243

AC:

1071

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0245

AC:

2972

Asia WGS

AF:

0.0140

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000889

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.11

DANN

Benign

0.88

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.34

T;T

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.49

N;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.12

N;N

REVEL

Benign

0.019

Sift

Benign

0.18

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0

B;B

Vest4

0.045

MPC

0.18

ClinPred

0.00083

GERP RS

-1.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.036

gMVP

0.43

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