rs1057517682
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Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PVS1_StrongPM2PP3PP5_Moderate
The NM_207421.4(PADI6):c.2009_2010del(p.Glu670GlyfsTer48) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,710 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
PADI6
NM_207421.4 frameshift
NM_207421.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.522
Genes affected
PADI6 (HGNC:20449): (peptidyl arginine deiminase 6) This gene encodes a member of the peptidyl arginine deiminase family of enzymes, which catalyze the post-translational deimination of proteins by converting arginine residues into citrullines in the presence of calcium ions. The family members have distinct substrate specificities and tissue-specific expression patterns. This protein may play a role in cytoskeletal reorganization in the egg and in early embryo development. [provided by RefSeq, Sep 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.519 CDS is truncated, and there are 1 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
PP5
?
Variant 1-17401359-CAG-C is Pathogenic according to our data. Variant chr1-17401359-CAG-C is described in ClinVar as [Pathogenic]. Clinvar id is 372229.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-17401359-CAG-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PADI6 | NM_207421.4 | c.2009_2010del | p.Glu670GlyfsTer48 | frameshift_variant | 16/16 | ENST00000619609.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PADI6 | ENST00000619609.1 | c.2009_2010del | p.Glu670GlyfsTer48 | frameshift_variant | 16/16 | 1 | NM_207421.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461710Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727136
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
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Bravo
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Preimplantation embryonic lethality 2 Pathogenic:2
Pathogenic, criteria provided, single submitter | case-control | Wang Lab, The Lab for Reproductive Genetics, Fudan University | Nov 01, 2021 | - - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 10, 2023 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 5
Find out detailed SpliceAI scores and Pangolin per-transcript scores at