rs797045778
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM1PM2PM4_Supporting
The NM_133433.4(NIPBL):c.6705_6707delAAA(p.Lys2235del) variant causes a disruptive inframe deletion 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 Uncertain significance (★★).
Frequency
Genomes: not found (cov: 32)
Consequence
NIPBL
NM_133433.4 disruptive_inframe_deletion
NM_133433.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.91
Genes affected
NIPBL (HGNC:28862): (NIPBL cohesin loading factor) This gene encodes the homolog of the Drosophila melanogaster Nipped-B gene product and fungal Scc2-type sister chromatid cohesion proteins. The Drosophila protein facilitates enhancer-promoter communication of remote enhancers and plays a role in developmental regulation. It is also homologous to a family of chromosomal adherins with broad roles in sister chromatid cohesion, chromosome condensation, and DNA repair. The human protein has a bipartite nuclear targeting sequence and a putative HEAT repeat. Condensins, cohesins and other complexes with chromosome-related functions also contain HEAT repeats. Mutations in this gene result in Cornelia de Lange syndrome, a disorder characterized by dysmorphic facial features, growth delay, limb reduction defects, and cognitive disability. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 5 ACMG points.
PM1
In a repeat HEAT 4 (size 40) in uniprot entity NIPBL_HUMAN there are 4 pathogenic changes around while only 0 benign (100%) in NM_133433.4
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_133433.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| NIPBL | ENST00000282516.13 | c.6705_6707delAAA | p.Lys2235del | disruptive_inframe_deletion | Exon 39 of 47 | 1 | NM_133433.4 | ENSP00000282516.8 | ||
| NIPBL | ENST00000448238.2 | c.6705_6707delAAA | p.Lys2235del | disruptive_inframe_deletion | Exon 39 of 46 | 1 | ENSP00000406266.2 | |||
| NIPBL | ENST00000652901.1 | c.6705_6707delAAA | p.Lys2235del | disruptive_inframe_deletion | Exon 39 of 46 | ENSP00000499536.1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Cornelia de Lange syndrome 1 Uncertain:2
Apr 08, 2021
Revvity Omics, Revvity
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
May 28, 2021
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research
ACMG codes:PM2; PP4 -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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
Publications
No publications associated with this variant yet.