1-17381046-G-GA
Variant summary
Our verdict is Pathogenic. Variant got 13 ACMG points: 13P and 0B. PVS1PM2PP3_ModeratePP5
The NM_207421.4(PADI6):c.441dup(p.Trp148MetfsTer20) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000691 in 1,592,250 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_207421.4 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PADI6 | NM_207421.4 | c.441dup | p.Trp148MetfsTer20 | frameshift_variant, splice_region_variant | ENST00000619609.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PADI6 | ENST00000619609.1 | c.441dup | p.Trp148MetfsTer20 | frameshift_variant, splice_region_variant | 1 | NM_207421.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000928 AC: 2AN: 215506Hom.: 0 AF XY: 0.0000172 AC XY: 2AN XY: 116350
GnomAD4 exome AF: 0.00000625 AC: 9AN: 1440148Hom.: 0 Cov.: 30 AF XY: 0.00000700 AC XY: 5AN XY: 714436
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74296
ClinVar
Submissions by phenotype
PADI6-related disorder Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | May 29, 2024 | The PADI6 c.441dupA variant is predicted to result in a frameshift and premature protein termination (p.Trp148Metfs*20). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0032% of alleles in individuals of Latino descent in gnomAD. Frameshift variants in PADI6 are expected to be pathogenic. This variant is interpreted as likely pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at