rs1060502840
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001159702.3(FHL1):c.60del(p.Gln21LysfsTer9) 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 (★). Synonymous variant affecting the same amino acid position (i.e. V20V) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 24)
Consequence
FHL1
NM_001159702.3 frameshift
NM_001159702.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.36
Genes affected
FHL1 (HGNC:3702): (four and a half LIM domains 1) This gene encodes a member of the four-and-a-half-LIM-only protein family. Family members contain two highly conserved, tandemly arranged, zinc finger domains with four highly conserved cysteines binding a zinc atom in each zinc finger. Expression of these family members occurs in a cell- and tissue-specific mode and these proteins are involved in many cellular processes. Mutations in this gene have been found in patients with Emery-Dreifuss muscular dystrophy. Multiple alternately spliced transcript variants which encode different protein isoforms have been described.[provided by RefSeq, Nov 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 does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 56 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-136206491-TG-T is Pathogenic according to our data. Variant chrX-136206491-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 410317.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FHL1 | NM_001159702.3 | c.60del | p.Gln21LysfsTer9 | frameshift_variant | 3/8 | ENST00000394155.8 | |
FHL1 | NM_001159699.2 | c.108del | p.Gln37LysfsTer9 | frameshift_variant | 2/6 | ENST00000370683.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FHL1 | ENST00000394155.8 | c.60del | p.Gln21LysfsTer9 | frameshift_variant | 3/8 | 5 | NM_001159702.3 | ||
FHL1 | ENST00000370683.6 | c.108del | p.Gln37LysfsTer9 | frameshift_variant | 2/6 | 1 | NM_001159699.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
X-linked myopathy with postural muscle atrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 06, 2020 | This sequence change creates a premature translational stop signal (p.Gln21Lysfs*9) in the FHL1 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in FHL1 are known to be pathogenic (PMID: 18179888, 19687455, 19716112, 22523091, 24114807). This variant has not been reported in the literature in individuals with FHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 410317). This variant is not present in population databases (ExAC no frequency). - |
Computational scores
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Calibrated prediction
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Prediction
Splicing
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Calibrated prediction
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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