rs587779348
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_014171.6(CRIPT):c.141del(p.Phe47LeufsTer84) variant causes a frameshift, splice region change. 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 Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CRIPT
NM_014171.6 frameshift, splice_region
NM_014171.6 frameshift, splice_region
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.98
Genes affected
CRIPT (HGNC:14312): (CXXC repeat containing interactor of PDZ3 domain) This gene encodes a protein that binds to the PDZ3 peptide recognition domain. The encoded protein may modulates protein interactions with the cytoskeleton. A mutation in this gene resulted in short stature with microcephaly and distinctive facies. [provided by RefSeq, Jun 2014]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 2-46623764-AT-A is Pathogenic according to our data. Variant chr2-46623764-AT-A is described in ClinVar as [Pathogenic]. Clinvar id is 127250.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-46623764-AT-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CRIPT | NM_014171.6 | c.141del | p.Phe47LeufsTer84 | frameshift_variant, splice_region_variant | 4/5 | ENST00000238892.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CRIPT | ENST00000238892.4 | c.141del | p.Phe47LeufsTer84 | frameshift_variant, splice_region_variant | 4/5 | 1 | NM_014171.6 | P1 | |
CRIPT | ENST00000486447.1 | n.733del | splice_region_variant, non_coding_transcript_exon_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1436542Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 715598
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
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0
AN:
1436542
Hom.:
Cov.:
26
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AC XY:
0
AN XY:
715598
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Ateleiotic dwarfism Pathogenic:1
Pathogenic, no assertion criteria provided | research | Department Of Translational Genomics (developmental Genetics Section), King Faisal Specialist Hospital & Research Centre | - | - - |
Short stature with microcephaly and distinctive facies Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 01, 2014 | - - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at