rs141168279

Variant names:

• chr9-136412069-A-C
• rs141168279
• NM_015160.3:c.144A>C

Your query was ambiguous. Multiple possible variants found:

• chr9-136412069-A-C
• chr9-136412069-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015160.3(PMPCA):​c.144A>C​(p.Leu48Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PMPCA NM_015160.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236

Genes affected

PMPCA (HGNC:18667): (peptidase, mitochondrial processing subunit alpha) The protein encoded by this gene is found in the mitochondrion, where it represents the alpha subunit of a proteolytic heterodimer. This heterodimer is responsible for cleaving the transit peptide from nuclear-encoded mitochondrial proteins. Defects in this gene are a cause of spinocerebellar ataxia, autosomal recessive 2. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.299538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PMPCA	NM_015160.3	c.144A>C	p.Leu48Phe	missense_variant	Exon 2 of 13	ENST00000371717.8	NP_055975.1
PMPCA	XM_005266059.4	c.144A>C	p.Leu48Phe	missense_variant	Exon 2 of 12		XP_005266116.1
PMPCA	NM_001282946.2	c.-155A>C		5_prime_UTR_variant	Exon 2 of 13		NP_001269875.1
PMPCA	NM_001282944.2	c.-155A>C		5_prime_UTR_variant	Exon 2 of 12		NP_001269873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PMPCA	ENST00000371717.8	c.144A>C	p.Leu48Phe	missense_variant	Exon 2 of 13	1	NM_015160.3	ENSP00000360782.3

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	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	T
Eigen	Benign	0.0055
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.032	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.29		Loss of ubiquitination at K53 (P = 0.0675);
MVP		0.33
MPC		0.23
ClinPred		0.99	D
GERP RS		-3.0
Varity_R		0.31
gMVP		0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141168279; hg19: chr9-139306521;