rs778311238
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Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002662.5(PLD1):c.1484_1485del(p.Thr495ArgfsTer33) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
PLD1
NM_002662.5 frameshift
NM_002662.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.92
Genes affected
PLD1 (HGNC:9067): (phospholipase D1) This gene encodes a phosphatidylcholine-specific phospholipase which catalyzes the hydrolysis of phosphatidylcholine in order to yield phosphatidic acid and choline. The enzyme may play a role in signal transduction and subcellular trafficking. Alternative splicing results in multiple transcript variants with both catalytic and regulatory properties. [provided by RefSeq, Sep 2011]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 3-171688729-CTG-C is Pathogenic according to our data. Variant chr3-171688729-CTG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 426090.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-171688729-CTG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLD1 | NM_002662.5 | c.1484_1485del | p.Thr495ArgfsTer33 | frameshift_variant | 14/27 | ENST00000351298.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLD1 | ENST00000351298.9 | c.1484_1485del | p.Thr495ArgfsTer33 | frameshift_variant | 14/27 | 1 | NM_002662.5 | A1 | |
PLD1 | ENST00000356327.9 | c.1484_1485del | p.Thr495ArgfsTer33 | frameshift_variant | 14/26 | 1 | P4 | ||
PLD1 | ENST00000481505.1 | n.455_456del | non_coding_transcript_exon_variant | 4/4 | 4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251390Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135858
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GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461878Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727246
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cardiac valvular defect, developmental Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 30, 2022 | - - |
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Sep 01, 2021 | - - |
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