rs587777853
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001166114.2(PNPLA6):c.1243dup(p.Asp415GlyfsTer18) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000481 in 1,454,156 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
PNPLA6
NM_001166114.2 frameshift
NM_001166114.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.81
Genes affected
PNPLA6 (HGNC:16268): (patatin like phospholipase domain containing 6) This gene encodes a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells. Mutations in this gene result in autosomal recessive spastic paraplegia, and the protein is the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-7542054-A-AG is Pathogenic according to our data. Variant chr19-7542054-A-AG is described in ClinVar as [Pathogenic]. Clinvar id is 156538.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA6 | NM_001166114.2 | c.1243dup | p.Asp415GlyfsTer18 | frameshift_variant | 10/32 | ENST00000600737.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA6 | ENST00000600737.6 | c.1243dup | p.Asp415GlyfsTer18 | frameshift_variant | 10/32 | 1 | NM_001166114.2 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000481 AC: 7AN: 1454156Hom.: 0 Cov.: 33 AF XY: 0.00000691 AC XY: 5AN XY: 723680
GnomAD4 exome
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7
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1454156
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33
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5
AN XY:
723680
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Ataxia-hypogonadism-choroidal dystrophy syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 01, 2014 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at