7-103297673-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004279.3(PMPCB):c.99+115C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,541,956 control chromosomes in the GnomAD database, including 178 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0089 (13 hom., cov: 33)
  • Exomes 𝑓: 0.014 (165 hom.)
• Consequence: PMPCB NM_004279.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.76

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-103297673-C-T is Benign according to our data. Variant chr7-103297673-C-T is described in ClinVar as [Benign]. Clinvar id is 1701532.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00887 (1350/152252) while in subpopulation NFE AF= 0.0139 (948/68002). AF 95% confidence interval is 0.0132. There are 13 homozygotes in gnomad4. There are 661 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMPCB	NM_004279.3	c.99+115C>T		intron_variant		ENST00000249269.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMPCB	ENST00000249269.9	c.99+115C>T		intron_variant		1	NM_004279.3	P1

Frequencies

GnomAD3 genomes AF: 0.00887 AC: 1350 AN: 152134 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00621

GnomAD3 exomes AF: 0.00888 AC: 1256 AN: 141368 Hom.: 9 AF XY: 0.00975 AC XY: 745 AN XY: 76448

Gnomad AFR exome AF: 0.00172

Gnomad AMR exome AF: 0.00231

Gnomad ASJ exome AF: 0.00229

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00865

Gnomad FIN exome AF: 0.0126

Gnomad NFE exome AF: 0.0151

Gnomad OTH exome AF: 0.00693

GnomAD4 exome AF: 0.0139 AC: 19273 AN: 1389704 Hom.: 165 Cov.: 31 AF XY: 0.0137 AC XY: 9392 AN XY: 685934

Gnomad4 AFR exome AF: 0.00227

Gnomad4 AMR exome AF: 0.00258

Gnomad4 ASJ exome AF: 0.00219

Gnomad4 EAS exome AF: 0.0000279

Gnomad4 SAS exome AF: 0.00818

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.0160

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.00887 AC: 1350 AN: 152252 Hom.: 13 Cov.: 33 AF XY: 0.00888 AC XY: 661 AN XY: 74428

Gnomad4 AFR AF: 0.00214

Gnomad4 AMR AF: 0.00229

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00706

Gnomad4 FIN AF: 0.0124

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.00615

Alfa AF: 0.00976 Hom.: 0

Bravo AF: 0.00820

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

PMPCB: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	0.49
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs192846145; hg19: chr7-102938120;