chr19-49862397-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_007254.4(PNKP):c.1003G>T(p.Gly335Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000577 in 1,559,340 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G335S) has been classified as Uncertain significance.
Frequency
Consequence
NM_007254.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PNKP | NM_007254.4 | c.1003G>T | p.Gly335Cys | missense_variant | 11/17 | ENST00000322344.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PNKP | ENST00000322344.8 | c.1003G>T | p.Gly335Cys | missense_variant | 11/17 | 1 | NM_007254.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152098Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000497 AC: 7AN: 1407128Hom.: 0 Cov.: 37 AF XY: 0.00000864 AC XY: 6AN XY: 694824
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74422
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 17, 2013 | p.Gly335Cys (GGC>TGC): c.1003 G>T in exon 11 of the PNKP gene (NM_007254.2) The Gly335Cys missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,400 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a non-polar Glycine residue is replaced by a polar Cysteine residue, and the gain of a Cysteine may affect disulfide bond formation in the protein. However, it alters a poorly conserved position in the protein, and multiple in silico algorithms predict it may be benign. Therefore, based on the currently available information, it is unclear whether Gly335Cys is a disease-causing mutation or a rare benign variant.The variant is found in EPILEPSY panel(s). - |
Microcephaly, seizures, and developmental delay;C4225397:Ataxia - oculomotor apraxia type 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at