rs587783973
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_133433.4(NIPBL):c.5389_5392delTCTG(p.Ser1797ArgfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_133433.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NIPBL | ENST00000282516.13 | c.5389_5392delTCTG | p.Ser1797ArgfsTer5 | frameshift_variant | Exon 28 of 47 | 1 | NM_133433.4 | ENSP00000282516.8 | ||
NIPBL | ENST00000448238.2 | c.5389_5392delTCTG | p.Ser1797ArgfsTer5 | frameshift_variant | Exon 28 of 46 | 1 | ENSP00000406266.2 | |||
NIPBL | ENST00000652901.1 | c.5389_5392delTCTG | p.Ser1797ArgfsTer5 | frameshift_variant | Exon 28 of 46 | ENSP00000499536.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cornelia de Lange syndrome 1 Pathogenic:2
This sequence change creates a premature translational stop signal (p.Ser1797Argfs*5) in the NIPBL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NIPBL are known to be pathogenic (PMID: 15318302, 19763162, 23505322, 29995837). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NIPBL-related conditions. ClinVar contains an entry for this variant (Variation ID: 159148). For these reasons, this variant has been classified as Pathogenic. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at