X-136207050-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001159699.2(FHL1):c.239C>T(p.Thr80Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000165 in 1,209,993 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T80N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001159699.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FHL1 | ENST00000394155.8 | c.191C>T | p.Thr64Ile | missense_variant | Exon 4 of 8 | 5 | NM_001159702.3 | ENSP00000377710.2 | ||
FHL1 | ENST00000370683.6 | c.239C>T | p.Thr80Ile | missense_variant | Exon 3 of 6 | 1 | NM_001159699.2 | ENSP00000359717.1 |
Frequencies
GnomAD3 genomes AF: 0.00000893 AC: 1AN: 112012Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34214
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183137Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67645
GnomAD4 exome AF: 9.11e-7 AC: 1AN: 1097981Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 1AN XY: 363407
GnomAD4 genome AF: 0.00000893 AC: 1AN: 112012Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34214
ClinVar
Submissions by phenotype
X-linked myopathy with postural muscle atrophy Uncertain:1
This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 64 of the FHL1 protein (p.Thr64Ile). This variant is present in population databases (rs746834335, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with FHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 581366). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at