9-136410674-G-C

Variant names:

• chr9-136410674-G-C
• rs372181000
• NM_015160.3:c.6G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_015160.3(PMPCA):​c.6G>C​(p.Ala2Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000793 in 1,261,718 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. Synonymous variant affecting the same amino acid position (i.e. A2A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.9e-7 (0 hom.)
• Consequence: PMPCA NM_015160.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP7: Synonymous conserved (PhyloP=2.6 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015160.3. 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
	PMPCA	NM_015160.3	MANE Select	c.6G>C	p.Ala2Ala	synonymous	Exon 1 of 13	NP_055975.1	Q10713-1
	PMPCA	NM_001282946.2		c.-293G>C		5_prime_UTR	Exon 1 of 13	NP_001269875.1
	PMPCA	NM_001282944.2		c.-293G>C		5_prime_UTR	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.6G>C	p.Ala2Ala	synonymous	Exon 1 of 13	ENSP00000360782.3	Q10713-1
	PMPCA	ENST00000622209.4	TSL:1	n.15G>C		non_coding_transcript_exon	Exon 1 of 5
	PMPCA	ENST00000444897.3	TSL:2	c.6G>C	p.Ala2Ala	synonymous	Exon 1 of 12	ENSP00000408393.2	Q5SXN9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.93e-7 AC: 1 AN: 1261718 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 619614

African (AFR) AF: 0.00 AC: 0 AN: 25674

American (AMR) AF: 0.00 AC: 0 AN: 17768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19242

East Asian (EAS) AF: 0.00 AC: 0 AN: 30956

South Asian (SAS) AF: 0.0000183 AC: 1 AN: 54714

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39806

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5030

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1017700

Other (OTH) AF: 0.00 AC: 0 AN: 50828

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	12
DANN	Benign	0.81
PhyloP100		2.6
PromoterAI		-0.024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7

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: rs372181000; hg19: chr9-139305126;