rs774909110
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_001166114.2(PNPLA6):āc.2907T>Cā(p.Ile969=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000401 in 1,473,066 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 Likely benign (ā ).
Frequency
Genomes: š 0.000049 ( 0 hom., cov: 32)
Exomes š: 0.000039 ( 1 hom. )
Consequence
PNPLA6
NM_001166114.2 synonymous
NM_001166114.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.794
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 -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant 19-7555338-T-C is Benign according to our data. Variant chr19-7555338-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 537339.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.794 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNPLA6 | NM_001166114.2 | c.2907T>C | p.Ile969= | synonymous_variant | 23/32 | ENST00000600737.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNPLA6 | ENST00000600737.6 | c.2907T>C | p.Ile969= | synonymous_variant | 23/32 | 1 | NM_001166114.2 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000494 AC: 7AN: 141706Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000132 AC: 23AN: 174558Hom.: 0 AF XY: 0.000139 AC XY: 13AN XY: 93454
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GnomAD4 exome AF: 0.0000391 AC: 52AN: 1331360Hom.: 1 Cov.: 34 AF XY: 0.0000471 AC XY: 31AN XY: 658578
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GnomAD4 genome ? AF: 0.0000494 AC: 7AN: 141706Hom.: 0 Cov.: 32 AF XY: 0.0000582 AC XY: 4AN XY: 68682
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 39 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at