rs2301861

Variant names:

• chr7-103297437-C-T
• rs2301861
• NM_004279.3:c.-23C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.897
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• multiple mitochondrial dysfunctions syndrome 6

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 1179481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004279.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMPCB	NM_004279.3	MANE Select	c.-23C>T		5_prime_UTR	Exon 1 of 13	NP_004270.2	O75439
	PMPCB	NM_001438231.1		c.-23C>T		5_prime_UTR	Exon 1 of 12	NP_001425160.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMPCB	ENST00000249269.9	TSL:1 MANE Select	c.-23C>T		5_prime_UTR	Exon 1 of 13	ENSP00000249269.4	O75439
	PMPCB	ENST00000428154.5	TSL:1	c.-23C>T		5_prime_UTR	Exon 1 of 12	ENSP00000390035.1	G3V0E4
	PMPCB	ENST00000706454.1		c.-23C>T		5_prime_UTR	Exon 1 of 13	ENSP00000516392.1	A0A9L9PXI7

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

GnomAD2 exomes AF: 0.0181 AC: 3486 AN: 192074 AF XY: 0.0178

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 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

African (AFR) AF: 0.000582 AC: 18 AN: 30940

American (AMR) AF: 0.000293 AC: 10 AN: 34158

Ashkenazi Jewish (ASJ) AF: 0.0000958 AC: 2 AN: 20876

East Asian (EAS) AF: 0.159 AC: 6128 AN: 38522

South Asian (SAS) AF: 0.00414 AC: 306 AN: 73834

European-Finnish (FIN) AF: 0.0510 AC: 2570 AN: 50414

Middle Eastern (MID) AF: 0.000783 AC: 3 AN: 3832

European-Non Finnish (NFE) AF: 0.000602 AC: 645 AN: 1071688

Other (OTH) AF: 0.00823 AC: 467 AN: 56724

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

African (AFR) AF: 0.00106 AC: 44 AN: 41582

American (AMR) AF: 0.00157 AC: 24 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.137 AC: 708 AN: 5172

South Asian (SAS) AF: 0.00725 AC: 35 AN: 4828

European-Finnish (FIN) AF: 0.0586 AC: 622 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00126 AC: 86 AN: 68030

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00204 Hom.: 12

Bravo AF: 0.00626

Asia WGS AF: 0.0500 AC: 172 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.0
DANN	Benign	0.79
PhyloP100		0.90
PromoterAI		0.076	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

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