chr5-157463151-AC-A
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Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The ENST00000311946.8(NIPAL4):c.97del(p.Leu33SerfsTer68) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
NIPAL4
ENST00000311946.8 frameshift
ENST00000311946.8 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.03
Genes affected
NIPAL4 (HGNC:28018): (NIPA like domain containing 4) This gene likely encodes a membrane receptor. Mutations in this gene have been associated with autosomal recessive congenital ichthyosis. [provided by RefSeq, Feb 2010]
ADAM19 (HGNC:197): (ADAM metallopeptidase domain 19) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This member is a type I transmembrane protein and serves as a marker for dendritic cell differentiation. It has been demonstrated to be an active metalloproteinase, which may be involved in normal physiological processes such as cell migration, cell adhesion, cell-cell and cell-matrix interactions, and signal transduction. It is proposed to play a role in pathological processes, such as cancer, inflammatory diseases, renal diseases, and Alzheimer's disease. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 26 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 5-157463151-AC-A is Pathogenic according to our data. Variant chr5-157463151-AC-A is described in ClinVar as [Pathogenic]. Clinvar id is 638535.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NIPAL4 | NM_001099287.2 | c.97del | p.Leu33SerfsTer68 | frameshift_variant | 2/6 | ENST00000311946.8 | NP_001092757.2 | |
NIPAL4 | NM_001172292.2 | c.97del | p.Leu33SerfsTer86 | frameshift_variant | 2/5 | NP_001165763.2 | ||
NIPAL4 | XM_011534552.2 | c.-213del | 5_prime_UTR_variant | 2/6 | XP_011532854.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NIPAL4 | ENST00000311946.8 | c.97del | p.Leu33SerfsTer68 | frameshift_variant | 2/6 | 1 | NM_001099287.2 | ENSP00000311687 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 6 Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Institute for Human Genetics, University Medical Center Freiburg | May 16, 2019 | - - |
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