rs2878

Variant names:

• chr7-103313174-A-G
• rs2878
• NM_004279.3:c.*903A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004279.3(PMPCB):​c.*903A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,497,770 control chromosomes in the GnomAD database, including 21,030 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.23 (6360 hom., cov: 32)
  • Exomes 𝑓: 0.13 (14670 hom.)
• Consequence: PMPCB NM_004279.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126
• Publications: 12 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]

DNAJC2 (HGNC:13192): (DnaJ heat shock protein family (Hsp40) member C2) This gene is a member of the M-phase phosphoprotein (MPP) family. The gene encodes a phosphoprotein with a J domain and a Myb DNA-binding domain which localizes to both the nucleus and the cytosol. The protein is capable of forming a heterodimeric complex that associates with ribosomes, acting as a molecular chaperone for nascent polypeptide chains as they exit the ribosome. This protein was identified as a leukemia-associated antigen and expression of the gene is upregulated in leukemic blasts. Also, chromosomal aberrations involving this gene are associated with primary head and neck squamous cell tumors. This gene has a pseudogene on chromosome 6. Alternatively spliced variants which encode different protein isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 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.*903A>G		3_prime_UTR	Exon 13 of 13	NP_004270.2
	DNAJC2	NM_014377.3	MANE Select	c.1637-73T>C		intron	N/A	NP_055192.1
	DNAJC2	NM_001129887.3		c.1478-73T>C		intron	N/A	NP_001123359.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMPCB	ENST00000249269.9	TSL:1 MANE Select	c.*903A>G		3_prime_UTR	Exon 13 of 13	ENSP00000249269.4
	DNAJC2	ENST00000379263.8	TSL:1 MANE Select	c.1637-73T>C		intron	N/A	ENSP00000368565.3
	DNAJC2	ENST00000249270.11	TSL:1	c.1478-73T>C		intron	N/A	ENSP00000249270.7

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34998 AN: 152034 Hom.: 6345 Cov.: 32

Gnomad AFR AF: 0.510

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.0806

Gnomad EAS AF: 0.0514

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.189

GnomAD4 exome AF: 0.132 AC: 178013 AN: 1345618 Hom.: 14670 Cov.: 32 AF XY: 0.131 AC XY: 86997 AN XY: 662750

African (AFR) AF: 0.536 AC: 15351 AN: 28654

American (AMR) AF: 0.196 AC: 5180 AN: 26412

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 1518 AN: 20358

East Asian (EAS) AF: 0.0603 AC: 2252 AN: 37350

South Asian (SAS) AF: 0.150 AC: 10002 AN: 66526

European-Finnish (FIN) AF: 0.147 AC: 6480 AN: 44008

Middle Eastern (MID) AF: 0.0964 AC: 456 AN: 4728

European-Non Finnish (NFE) AF: 0.121 AC: 128654 AN: 1062320

Other (OTH) AF: 0.147 AC: 8120 AN: 55262

GnomAD4 genome AF: 0.230 AC: 35050 AN: 152152 Hom.: 6360 Cov.: 32 AF XY: 0.227 AC XY: 16903 AN XY: 74386

African (AFR) AF: 0.510 AC: 21128 AN: 41436

American (AMR) AF: 0.170 AC: 2597 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0806 AC: 280 AN: 3472

East Asian (EAS) AF: 0.0506 AC: 262 AN: 5182

South Asian (SAS) AF: 0.137 AC: 664 AN: 4832

European-Finnish (FIN) AF: 0.146 AC: 1553 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8076 AN: 68018

Other (OTH) AF: 0.188 AC: 396 AN: 2112

Alfa AF: 0.181 Hom.: 1212

Bravo AF: 0.246

Asia WGS AF: 0.133 AC: 461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.61
DANN	Benign	0.65
PhyloP100		0.13
Mutation Taster		=100/0	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: rs2878; hg19: chr7-102953621;