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. Variant got 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. 13/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• 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=0.13344514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMPCB	NM_004279.3	c.8C>A	p.Ala3Asp	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>A	p.Ala3Asp	missense_variant	Exon 1 of 13	1	NM_004279.3	ENSP00000249269.4

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

Gnomad4 AFR exome AF: 0.0000321

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.29e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.91	N;N
REVEL	Benign	0.10
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.023	B;B
Vest4		0.48
MutPred		0.39		Loss of MoRF binding (P = 0.0523);Loss of MoRF binding (P = 0.0523);
MVP		0.19
MPC		0.20
ClinPred		0.84	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.63
gMVP		0.65

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: rs138251541; hg19: chr7-102937914;