NM_024782.3:c.860C>A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PVS1_ModeratePM2BS1_Supporting
The NM_024782.3(NHEJ1):c.860C>A(p.Ser287*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_024782.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NHEJ1 | NM_024782.3 | c.860C>A | p.Ser287* | stop_gained | Exon 8 of 8 | ENST00000356853.10 | NP_079058.1 | |
NHEJ1 | NM_001377499.1 | c.875C>A | p.Ser292* | stop_gained | Exon 8 of 8 | NP_001364428.1 | ||
NHEJ1 | NM_001377498.1 | c.860C>A | p.Ser287* | stop_gained | Exon 8 of 8 | NP_001364427.1 | ||
NHEJ1 | NR_165304.1 | n.1038C>A | non_coding_transcript_exon_variant | Exon 9 of 9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NHEJ1 | ENST00000356853.10 | c.860C>A | p.Ser287* | stop_gained | Exon 8 of 8 | 1 | NM_024782.3 | ENSP00000349313.5 | ||
ENSG00000280537 | ENST00000318673.6 | n.*1982C>A | non_coding_transcript_exon_variant | Exon 17 of 17 | 2 | ENSP00000320919.3 | ||||
ENSG00000280537 | ENST00000318673.6 | n.*1982C>A | 3_prime_UTR_variant | Exon 17 of 17 | 2 | ENSP00000320919.3 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249422Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135008
GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461874Hom.: 0 Cov.: 36 AF XY: 0.0000110 AC XY: 8AN XY: 727238
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152104Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74312
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: NHEJ1 c.860C>A (p.Ser287X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein. Truncations downstream of this position have not been classified as pathogenic by our laboratory or in ClinVar. The variant allele was found at a frequency of 1.2e-05 in 249422 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.860C>A in individuals affected with Severe Combined Immunodeficiency and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at