rs1553542017
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_024782.3(NHEJ1):c.643C>T(p.Gln215Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
NHEJ1
NM_024782.3 stop_gained
NM_024782.3 stop_gained
Scores
4
2
1
Clinical Significance
Conservation
PhyloP100: 5.25
Genes affected
NHEJ1 (HGNC:25737): (non-homologous end joining factor 1) Double-strand breaks in DNA result from genotoxic stresses and are among the most damaging of DNA lesions. This gene encodes a DNA repair factor essential for the nonhomologous end-joining pathway, which preferentially mediates repair of double-stranded breaks. Mutations in this gene cause different kinds of severe combined immunodeficiency disorders. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-219078152-G-A is Pathogenic according to our data. Variant chr2-219078152-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 536739.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NHEJ1 | NM_024782.3 | c.643C>T | p.Gln215Ter | stop_gained | 6/8 | ENST00000356853.10 | |
NHEJ1 | NM_001377499.1 | c.643C>T | p.Gln215Ter | stop_gained | 6/8 | ||
NHEJ1 | NM_001377498.1 | c.643C>T | p.Gln215Ter | stop_gained | 6/8 | ||
NHEJ1 | NR_165304.1 | n.821C>T | non_coding_transcript_exon_variant | 7/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NHEJ1 | ENST00000356853.10 | c.643C>T | p.Gln215Ter | stop_gained | 6/8 | 1 | NM_024782.3 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Alfa
AF:
Hom.:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cernunnos-XLF deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 17, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NHEJ1 are known to be pathogenic (PMID: 16439204, 20597108). This variant has not been reported in the literature in individuals with NHEJ1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln215*) in the NHEJ1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at