9-136410684-C-T

Variant names:

• chr9-136410684-C-T
• rs751427408
• NM_015160.3:c.16C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282946.2(PMPCA):​c.-283C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000792 in 1,263,326 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: PMPCA NM_001282946.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• Publications: 1 publications found

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]

ENTR1 (HGNC:10667): (endosome associated trafficking regulator 1) Involved in several processes, including endocytic recycling; positive regulation of cilium assembly; and positive regulation of protein localization to cilium. Located in endosome; microtubule organizing center; and midbody. Colocalizes with retromer complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282946.2. 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
	PMPCA	NM_015160.3	MANE Select	c.16C>T	p.Leu6Leu	synonymous	Exon 1 of 13	NP_055975.1	Q10713-1
	PMPCA	NM_001282946.2		c.-283C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	NP_001269875.1
	PMPCA	NM_001282944.2		c.-283C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 12	NP_001269873.1	Q10713-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PMPCA	ENST00000371717.8	TSL:1 MANE Select	c.16C>T	p.Leu6Leu	synonymous	Exon 1 of 13	ENSP00000360782.3	Q10713-1
	PMPCA	ENST00000622209.4	TSL:1	n.25C>T		non_coding_transcript_exon	Exon 1 of 5
	PMPCA	ENST00000444897.3	TSL:2	c.16C>T	p.Leu6Leu	synonymous	Exon 1 of 12	ENSP00000408393.2	Q5SXN9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.92e-7 AC: 1 AN: 1263326 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 620538

African (AFR) AF: 0.00 AC: 0 AN: 25654

American (AMR) AF: 0.00 AC: 0 AN: 17908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19522

East Asian (EAS) AF: 0.00 AC: 0 AN: 30942

South Asian (SAS) AF: 0.00 AC: 0 AN: 55716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 9.82e-7 AC: 1 AN: 1018316

Other (OTH) AF: 0.00 AC: 0 AN: 50876

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.0
DANN	Benign	0.88
PhyloP100		-3.2
PromoterAI		0.017	Neutral

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: rs751427408; hg19: chr9-139305136;