rs933246467
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM2PP3_ModerateBS2
The NM_025219.3(DNAJC5):c.242C>T(p.Ser81Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S81S) has been classified as Likely benign.
Frequency
Consequence
NM_025219.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJC5 | NM_025219.3 | c.242C>T | p.Ser81Leu | missense_variant | 3/5 | ENST00000360864.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJC5 | ENST00000360864.9 | c.242C>T | p.Ser81Leu | missense_variant | 3/5 | 1 | NM_025219.3 | P1 | |
DNAJC5 | ENST00000470551.1 | c.242C>T | p.Ser81Leu | missense_variant, NMD_transcript_variant | 3/6 | 2 | |||
DNAJC5 | ENST00000703637.1 | c.242C>T | p.Ser81Leu | missense_variant, NMD_transcript_variant | 3/6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461848Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727222
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Neuronal ceroid lipofuscinosis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2018 | 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: "Probably Damaging"; Align-GVGD: "Class C0"). Family studies have indicated that an individual with epilepsy inherited this variant from an unaffected parent, which suggests that this variant is not likely a primary cause of disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with leucine at codon 81 of the DNAJC5 protein (p.Ser81Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. 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