chr18-31386726-GCAAA-G
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_177986.5(DSG4):c.126_129del(p.Thr43SerfsTer40) variant causes a frameshift change. The variant allele was found at a frequency of 0.00000205 in 1,461,142 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 0.0000021 ( 1 hom. )
Consequence
DSG4
NM_177986.5 frameshift
NM_177986.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.89
Genes affected
DSG4 (HGNC:21307): (desmoglein 4) This gene encodes a member of the desmoglein subgroup of desmosomal cadherins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a transmembrane component of desmosomes and may play a role in cell-cell adhesion in epithelial cells. Mutations in the gene are associated with localized autosomal recessive hypotrichosis and monilethrix, characterized by impaired hair growth. [provided by RefSeq, May 2016]
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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 18-31386726-GCAAA-G is Pathogenic according to our data. Variant chr18-31386726-GCAAA-G is described in ClinVar as [Pathogenic]. Clinvar id is 2502918.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DSG4 | NM_177986.5 | c.126_129del | p.Thr43SerfsTer40 | frameshift_variant | 3/16 | ENST00000308128.9 | |
DSG1-AS1 | NR_110788.1 | n.157-32277_157-32274del | intron_variant, non_coding_transcript_variant | ||||
DSG4 | NM_001134453.3 | c.126_129del | p.Thr43SerfsTer40 | frameshift_variant | 3/15 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DSG4 | ENST00000308128.9 | c.126_129del | p.Thr43SerfsTer40 | frameshift_variant | 3/16 | 1 | NM_177986.5 | P2 | |
DSG1-AS1 | ENST00000581856.5 | n.96-32277_96-32274del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461142Hom.: 1 AF XY: 0.00000138 AC XY: 1AN XY: 726874
GnomAD4 exome
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3
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726874
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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
Hypotrichosis 6 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 26, 2023 | - - |
Computational scores
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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
Publications
No publications associated with this variant yet.