chr20-6075642-C-T
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting
The NM_017671.5(FERMT1):c.*1531G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000729 in 152,164 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00073 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FERMT1
NM_017671.5 3_prime_UTR
NM_017671.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.65
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 Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000729 (111/152164) while in subpopulation AFR AF= 0.00219 (91/41514). AF 95% confidence interval is 0.00183. There are 1 homozygotes in gnomad4. There are 48 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FERMT1 | NM_017671.5 | c.*1531G>A | 3_prime_UTR_variant | 15/15 | ENST00000217289.9 | NP_060141.3 | ||
FERMT1 | XM_024451935.2 | c.*1531G>A | 3_prime_UTR_variant | 15/15 | XP_024307703.1 | |||
FERMT1 | XM_047440259.1 | c.*1531G>A | 3_prime_UTR_variant | 15/15 | XP_047296215.1 | |||
FERMT1 | XM_047440260.1 | c.*1531G>A | 3_prime_UTR_variant | 14/14 | XP_047296216.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FERMT1 | ENST00000217289.9 | c.*1531G>A | 3_prime_UTR_variant | 15/15 | 1 | NM_017671.5 | ENSP00000217289 | P1 | ||
FERMT1 | ENST00000478194.1 | n.2525G>A | non_coding_transcript_exon_variant | 7/7 | 1 | |||||
FERMT1 | ENST00000699095.1 | c.*1531G>A | 3_prime_UTR_variant | 14/14 | ENSP00000514127 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000730 AC: 111AN: 152046Hom.: 1 Cov.: 32
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GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 156Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 92
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GnomAD4 genome AF: 0.000729 AC: 111AN: 152164Hom.: 1 Cov.: 32 AF XY: 0.000645 AC XY: 48AN XY: 74398
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Kindler syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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