11-73969996-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PM5PP3
The NM_153614.4(DNAJB13):āc.833T>Cā(p.Met278Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,611,588 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 (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M278R) has been classified as Pathogenic.
Frequency
Consequence
NM_153614.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAJB13 | NM_153614.4 | c.833T>C | p.Met278Thr | missense_variant | 8/8 | ENST00000339764.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAJB13 | ENST00000339764.6 | c.833T>C | p.Met278Thr | missense_variant | 8/8 | 1 | NM_153614.4 | P1 | |
DNAJB13 | ENST00000543947.1 | c.308T>C | p.Met103Thr | missense_variant | 5/6 | 1 | |||
DNAJB13 | ENST00000542350.5 | c.536T>C | p.Met179Thr | missense_variant | 5/5 | 3 | |||
DNAJB13 | ENST00000537753.5 | c.308T>C | p.Met103Thr | missense_variant | 5/5 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000648 AC: 16AN: 247094Hom.: 0 AF XY: 0.0000598 AC XY: 8AN XY: 133774
GnomAD4 exome AF: 0.0000267 AC: 39AN: 1459400Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 725820
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74342
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 24, 2022 | 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with DNAJB13-related conditions. This variant is present in population databases (rs754776389, gnomAD 0.05%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 278 of the DNAJB13 protein (p.Met278Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at