19-49861317-C-T
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_007254.4(PNKP):c.1497G>A(p.Leu499Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000735 in 1,614,164 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L499L) has been classified as Likely benign.
Frequency
Consequence
NM_007254.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00215 AC: 327AN: 152208Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000907 AC: 228AN: 251380Hom.: 0 AF XY: 0.000751 AC XY: 102AN XY: 135900
GnomAD4 exome AF: 0.000588 AC: 859AN: 1461838Hom.: 2 Cov.: 33 AF XY: 0.000538 AC XY: 391AN XY: 727220
GnomAD4 genome AF: 0.00215 AC: 328AN: 152326Hom.: 1 Cov.: 32 AF XY: 0.00208 AC XY: 155AN XY: 74482
ClinVar
Submissions by phenotype
not specified Benign:3
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:3
PNKP: BP4, BP7 -
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Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
PNKP-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Developmental and epileptic encephalopathy, 12 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at