Variant chr7-103299440-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004279.3(PMPCB):c.241-3A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0254 in 1,567,602 control chromosomes in the GnomAD database, including 610 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 49 hom., cov: 33)

Exomes 𝑓: 0.026 ( 561 hom. )

Consequence

PMPCB
NM_004279.3 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.1295

Clinical Significance

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

Conservation

PhyloP100: -0.975

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 7-103299440-A-G is Benign according to our data. Variant chr7-103299440-A-G is described in ClinVar as [Benign]. Clinvar id is 1280327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.021 (3195/152320) while in subpopulation NFE AF= 0.0294 (2001/68030). AF 95% confidence interval is 0.0283. There are 49 homozygotes in gnomad4. There are 1609 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMPCB	NM_004279.3 linkuse as main transcript	c.241-3A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000249269.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMPCB	ENST00000249269.9 linkuse as main transcript	c.241-3A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004279.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0210

AC:

3197

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00458

Gnomad AMI

AF:

0.0945

Gnomad AMR

AF:

0.0105

Gnomad ASJ

AF:

0.0262

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.0526

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0294

Gnomad OTH

AF:

0.00956

GnomAD3 exomes

AF:

0.0219

AC:

5392

AN:

246254

Hom.:

105

AF XY:

0.0227

AC XY:

3027

AN XY:

133084

show subpopulations

Gnomad AFR exome

AF:

0.00427

Gnomad AMR exome

AF:

0.00732

Gnomad ASJ exome

AF:

0.0254

Gnomad EAS exome

AF:

0.0000552

Gnomad SAS exome

AF:

0.0195

Gnomad FIN exome

AF:

0.0508

Gnomad NFE exome

AF:

0.0271

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0259

AC:

36648

AN:

1415282

Hom.:

561

Cov.:

AF XY:

0.0258

AC XY:

18203

AN XY:

706670

show subpopulations

Gnomad4 AFR exome

AF:

0.00384

Gnomad4 AMR exome

AF:

0.00833

Gnomad4 ASJ exome

AF:

0.0251

Gnomad4 EAS exome

AF:

0.0000507

Gnomad4 SAS exome

AF:

0.0203

Gnomad4 FIN exome

AF:

0.0468

Gnomad4 NFE exome

AF:

0.0280

Gnomad4 OTH exome

AF:

0.0217

GnomAD4 genome

AF:

0.0210

AC:

3195

AN:

152320

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1609

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00457

Gnomad4 AMR

AF:

0.0105

Gnomad4 ASJ

AF:

0.0262

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0176

Gnomad4 FIN

AF:

0.0526

Gnomad4 NFE

AF:

0.0294

Gnomad4 OTH

AF:

0.00946

Alfa

AF:

0.0252

Hom.:

Bravo

AF:

0.0173

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0248

EpiControl

AF:

0.0224

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	GeneDx	May 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.5

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.13

dbscSNV1_RF

Benign

0.39

SpliceAI score (max)

0.040

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