chr7-103297467-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004279.3(PMPCB):​c.8C>G​(p.Ala3Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PMPCB NM_004279.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10160336).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMPCB	NM_004279.3	c.8C>G	p.Ala3Gly	missense_variant	Exon 1 of 13	ENST00000249269.9	NP_004270.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMPCB	ENST00000249269.9	c.8C>G	p.Ala3Gly	missense_variant	Exon 1 of 13	1	NM_004279.3	ENSP00000249269.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.091	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.092	T;T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.77	N;N
REVEL	Benign	0.063
Sift	Uncertain	0.015	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.0050	B;B
Vest4		0.38
MutPred		0.39		Loss of helix (P = 0.0104);Loss of helix (P = 0.0104);
MVP		0.16
MPC		0.13
ClinPred		0.25	T
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.17
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-102937914;