chr8-89937027-TA-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_002485.5(NBN):βc.2232delβ(p.Phe744LeufsTer7) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (β β ). Synonymous variant affecting the same amino acid position (i.e. F744F) has been classified as Likely benign.
Frequency
Consequence
NM_002485.5 frameshift, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NBN | NM_002485.5 | c.2232del | p.Phe744LeufsTer7 | frameshift_variant, splice_region_variant | 15/16 | ENST00000265433.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NBN | ENST00000265433.8 | c.2232del | p.Phe744LeufsTer7 | frameshift_variant, splice_region_variant | 15/16 | 1 | NM_002485.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1456926Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 725088
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Microcephaly, normal intelligence and immunodeficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Nov 07, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 27, 2020 | In summary, this is a novel truncation with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Experimental studies have not been reported for this truncating variant and it is currently unknown if the last 11 amino acids of the NBN protein are critical for its function. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an NBN-related disease. This sequence change deletes 1 nucleotide from exon 15 of the NBN mRNA (c.2232delT), causing a frameshift at codon 744. This creates a premature translational stop signal in the last exon of the NBN mRNA (p.Phe744Leufs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acids of the NBN protein. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at