chr3-180984665-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_145261.4(DNAJC19):āc.326T>Cā(p.Leu109Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,456,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. L109V) has been classified as Uncertain significance.
Frequency
Consequence
NM_145261.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJC19 | NM_145261.4 | c.326T>C | p.Leu109Ser | missense_variant | 6/6 | ENST00000382564.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJC19 | ENST00000382564.8 | c.326T>C | p.Leu109Ser | missense_variant | 6/6 | 1 | NM_145261.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246642Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133398
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1456200Hom.: 0 Cov.: 29 AF XY: 0.00000690 AC XY: 5AN XY: 724442
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
3-methylglutaconic aciduria type 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 17, 2022 | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 109 of the DNAJC19 protein (p.Leu109Ser). This variant is present in population databases (rs200732155, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DNAJC19-related conditions. ClinVar contains an entry for this variant (Variation ID: 1502917). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at