rs201144113
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_001166114.2(PNPLA6):c.3699+9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000224 in 1,612,924 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00022 ( 1 hom. )
Consequence
PNPLA6
NM_001166114.2 intron
NM_001166114.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.462
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 19-7559160-G-A is Benign according to our data. Variant chr19-7559160-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 537337.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| PNPLA6 | NM_001166114.2 | c.3699+9G>A | intron_variant | ENST00000600737.6 | NP_001159586.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| PNPLA6 | ENST00000600737.6 | c.3699+9G>A | intron_variant | 1 | NM_001166114.2 | ENSP00000473211.1 |
Frequencies
GnomAD3 genomes 0.000230 AC: 35AN: 152206Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000478 AC: 120AN: 251052Hom.: 0 AF XY: 0.000457 AC XY: 62AN XY: 135750
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GnomAD4 exome AF: 0.000224 AC: 327AN: 1460718Hom.: 1 Cov.: 35 AF XY: 0.000238 AC XY: 173AN XY: 726774
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GnomAD4 genome 0.000230 AC: 35AN: 152206Hom.: 0 Cov.: 33 AF XY: 0.000229 AC XY: 17AN XY: 74348
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 39 Uncertain:1Benign:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
| Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 09, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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