rs121918292
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_017671.5(FERMT1):c.787C>T(p.Gln263*) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
FERMT1
NM_017671.5 stop_gained
NM_017671.5 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 4.66
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 20-6107594-G-A is Pathogenic according to our data. Variant chr20-6107594-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 2714.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-6107594-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FERMT1 | NM_017671.5 | c.787C>T | p.Gln263* | stop_gained | 6/15 | ENST00000217289.9 | NP_060141.3 | |
FERMT1 | XM_024451935.2 | c.787C>T | p.Gln263* | stop_gained | 6/15 | XP_024307703.1 | ||
FERMT1 | XM_047440259.1 | c.787C>T | p.Gln263* | stop_gained | 6/15 | XP_047296215.1 | ||
FERMT1 | XM_047440260.1 | c.502C>T | p.Gln168* | stop_gained | 5/14 | XP_047296216.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 29
GnomAD4 exome
Cov.:
29
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Kindler syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 15, 2003 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 16, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
Vest4
GERP RS
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