7-103297437-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004279.3(PMPCB):c.-23C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00762 in 1,533,296 control chromosomes in the GnomAD database, including 678 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (67 hom., cov: 33)
  • Exomes 𝑓: 0.0073 (611 hom.)
• Consequence: PMPCB NM_004279.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.897

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=-0.88).
• BP6: Variant 7-103297437-C-T is Benign according to our data. Variant chr7-103297437-C-T is described in ClinVar as [Benign]. Clinvar id is 1179481.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PMPCB	NM_004279.3	c.-23C>T		5_prime_UTR_variant	1/13	ENST00000249269.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PMPCB	ENST00000249269.9	c.-23C>T		5_prime_UTR_variant	1/13	1	NM_004279.3	P1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1534 AN: 152190 Hom.: 67 Cov.: 33

Gnomad AFR AF: 0.00106

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.00745

Gnomad FIN AF: 0.0586

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00126

Gnomad OTH AF: 0.00669

GnomAD3 exomes AF: 0.0181 AC: 3486 AN: 192074 Hom.: 211 AF XY: 0.0178 AC XY: 1810 AN XY: 101580

Gnomad AFR exome AF: 0.000852

Gnomad AMR exome AF: 0.000355

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.134

Gnomad SAS exome AF: 0.00394

Gnomad FIN exome AF: 0.0549

Gnomad NFE exome AF: 0.00201

Gnomad OTH exome AF: 0.0110

GnomAD4 exome AF: 0.00735 AC: 10149 AN: 1380988 Hom.: 611 Cov.: 31 AF XY: 0.00731 AC XY: 4954 AN XY: 677676

Gnomad4 AFR exome AF: 0.000582

Gnomad4 AMR exome AF: 0.000293

Gnomad4 ASJ exome AF: 0.0000958

Gnomad4 EAS exome AF: 0.159

Gnomad4 SAS exome AF: 0.00414

Gnomad4 FIN exome AF: 0.0510

Gnomad4 NFE exome AF: 0.000602

Gnomad4 OTH exome AF: 0.00823

GnomAD4 genome AF: 0.0101 AC: 1537 AN: 152308 Hom.: 67 Cov.: 33 AF XY: 0.0134 AC XY: 998 AN XY: 74470

Gnomad4 AFR AF: 0.00106

Gnomad4 AMR AF: 0.00157

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.137

Gnomad4 SAS AF: 0.00725

Gnomad4 FIN AF: 0.0586

Gnomad4 NFE AF: 0.00126

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00216 Hom.: 4

Bravo AF: 0.00626

Asia WGS AF: 0.0500 AC: 172 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

GeneDx

May 21, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.0
Dann	Benign	0.79

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: rs2301861; hg19: chr7-102937884; COSMIC: COSV50785820; COSMIC: COSV50785820;