rs869312723
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017671.5(FERMT1):c.373del(p.Cys125AlafsTer4) 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 Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
FERMT1
NM_017671.5 frameshift
NM_017671.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.43
Genes affected
FERMT1 (HGNC:15889): (FERM domain containing kindlin 1) This gene encodes a member of the fermitin family, and contains a FERM domain and a pleckstrin homology domain. The encoded protein is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Mutations in this gene have been linked to Kindler syndrome. [provided by RefSeq, Dec 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 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 20-6115822-CA-C is Pathogenic according to our data. Variant chr20-6115822-CA-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 2440238.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-6115822-CA-C is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FERMT1 | NM_017671.5 | c.373del | p.Cys125AlafsTer4 | frameshift_variant | 3/15 | ENST00000217289.9 | |
FERMT1 | XM_024451935.2 | c.373del | p.Cys125AlafsTer4 | frameshift_variant | 3/15 | ||
FERMT1 | XM_047440259.1 | c.373del | p.Cys125AlafsTer4 | frameshift_variant | 3/15 | ||
FERMT1 | XM_047440260.1 | c.88del | p.Cys30AlafsTer4 | frameshift_variant | 2/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FERMT1 | ENST00000217289.9 | c.373del | p.Cys125AlafsTer4 | frameshift_variant | 3/15 | 1 | NM_017671.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Kindler syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 13, 2022 | - - |
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