chr9-136418847-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM5PP3PP5
The NM_015160.3(PMPCA):c.1129G>A(p.Ala377Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,612,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A377V) has been classified as Likely pathogenic.
Frequency
Consequence
NM_015160.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PMPCA | NM_015160.3 | c.1129G>A | p.Ala377Thr | missense_variant | 10/13 | ENST00000371717.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PMPCA | ENST00000371717.8 | c.1129G>A | p.Ala377Thr | missense_variant | 10/13 | 1 | NM_015160.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152074Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250696Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135594
GnomAD4 exome AF: 0.00000753 AC: 11AN: 1460530Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726684
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152074Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74288
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy;C0020258:Normal pressure hydrocephalus;C0029124:Optic atrophy;C0241816:Global brain atrophy;C0456909:Blindness;C1837397:Severe global developmental delay;C1839437:Chronic lactic acidosis;C1854699:Diffuse cerebellar atrophy;C1860834:Infantile muscular hypotonia;C1865916:Bilateral ptosis;C1865918:Restrictive external ophthalmoplegia;C2315100:Failure to thrive;C3203358:Hypoventilation Pathogenic:1
Pathogenic, no assertion criteria provided | research | Gene Discovery Core-Manton Center, Boston Children's Hospital | Jan 22, 2016 | - - |
Autosomal recessive spinocerebellar ataxia 2 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 10, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at