chr10-63213845-T-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_032776.3(JMJD1C):āc.2322A>Cā(p.Leu774Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,752 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 (ā ).
Frequency
Consequence
NM_032776.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JMJD1C | NM_032776.3 | c.2322A>C | p.Leu774Phe | missense_variant | 8/26 | ENST00000399262.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JMJD1C | ENST00000399262.7 | c.2322A>C | p.Leu774Phe | missense_variant | 8/26 | 5 | NM_032776.3 | ||
JMJD1C | ENST00000542921.5 | c.1776A>C | p.Leu592Phe | missense_variant | 7/25 | 1 | P1 | ||
JMJD1C | ENST00000402544.5 | n.2294A>C | non_coding_transcript_exon_variant | 5/22 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152056Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249144Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135160
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461696Hom.: 0 Cov.: 33 AF XY: 0.00000688 AC XY: 5AN XY: 727160
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152056Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74266
ClinVar
Submissions by phenotype
Early myoclonic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 10, 2020 | In summary, this variant has uncertain impact on JMJD1C function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with a JMJD1C-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with phenylalanine at codon 774 of the JMJD1C protein (p.Leu774Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at