rs138251541

Variant names:

• chr7-103297467-C-A
• rs138251541
• NM_004279.3:c.8C>A

Your query was ambiguous. Multiple possible variants found:

• chr7-103297467-C-A
• chr7-103297467-C-G
• chr7-103297467-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004279.3(PMPCB):​c.8C>A​(p.Ala3Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000144 in 1,391,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A3V) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PMPCB NM_004279.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• 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: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13344514).

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.8C>A	p.Ala3Asp	missense	Exon 1 of 13	NP_004270.2	O75439
	PMPCB	NM_001438231.1		c.8C>A	p.Ala3Asp	missense	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.8C>A	p.Ala3Asp	missense	Exon 1 of 13	ENSP00000249269.4	O75439
	PMPCB	ENST00000428154.5	TSL:1	c.8C>A	p.Ala3Asp	missense	Exon 1 of 12	ENSP00000390035.1	G3V0E4
	PMPCB	ENST00000706454.1		c.8C>A	p.Ala3Asp	missense	Exon 1 of 13	ENSP00000516392.1	A0A9L9PXI7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1391272 Hom.: 0 Cov.: 31 AF XY: 0.00000146 AC XY: 1 AN XY: 684474

African (AFR) AF: 0.0000321 AC: 1 AN: 31140

American (AMR) AF: 0.00 AC: 0 AN: 35292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21482

East Asian (EAS) AF: 0.00 AC: 0 AN: 38580

South Asian (SAS) AF: 0.00 AC: 0 AN: 75836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50784

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4258

European-Non Finnish (NFE) AF: 9.29e-7 AC: 1 AN: 1076658

Other (OTH) AF: 0.00 AC: 0 AN: 57242

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.3
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.91	N
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.023	B
Vest4		0.48
MutPred		0.39		Loss of MoRF binding (P = 0.0523)
MVP		0.19
MPC		0.20
ClinPred		0.84	D
GERP RS		2.2
PromoterAI		-0.092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.63
gMVP		0.65
Mutation Taster		=93/7	polymorphism

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: rs138251541; hg19: chr7-102937914;