rs746786140
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_032776.3(JMJD1C):āc.2300G>Cā(p.Gly767Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,613,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G767R) has been classified as Uncertain significance.
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.2300G>C | p.Gly767Ala | missense_variant | 8/26 | ENST00000399262.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JMJD1C | ENST00000399262.7 | c.2300G>C | p.Gly767Ala | missense_variant | 8/26 | 5 | NM_032776.3 | ||
JMJD1C | ENST00000542921.5 | c.1754G>C | p.Gly585Ala | missense_variant | 7/25 | 1 | P1 | ||
JMJD1C | ENST00000402544.5 | n.2272G>C | non_coding_transcript_exon_variant | 5/22 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249306Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135260
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461790Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727202
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74282
ClinVar
Submissions by phenotype
Early myoclonic encephalopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 05, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with JMJD1C-related disease. This variant is present in population databases (rs746786140, ExAC 0.009%). This sequence change replaces glycine with alanine at codon 767 of the JMJD1C protein (p.Gly767Ala). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and alanine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at