chrX-136206438-G-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001159702.3(FHL1):c.6G>A(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000819 in 1,098,236 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 24)
Exomes 𝑓: 0.0000082 ( 0 hom. 2 hem. )
Consequence
FHL1
NM_001159702.3 synonymous
NM_001159702.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.54
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
?
Variant X-136206438-G-A is Benign according to our data. Variant chrX-136206438-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2450879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.54 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FHL1 | NM_001159702.3 | c.6G>A | p.Ala2= | synonymous_variant | 3/8 | ENST00000394155.8 | |
FHL1 | NM_001159699.2 | c.54G>A | p.Ala18= | synonymous_variant | 2/6 | ENST00000370683.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FHL1 | ENST00000394155.8 | c.6G>A | p.Ala2= | synonymous_variant | 3/8 | 5 | NM_001159702.3 | ||
FHL1 | ENST00000370683.6 | c.54G>A | p.Ala18= | synonymous_variant | 2/6 | 1 | NM_001159699.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 24
GnomAD3 genomes
?
Cov.:
24
GnomAD4 exome AF: 0.00000819 AC: 9AN: 1098236Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 2AN XY: 363592
GnomAD4 exome
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AC:
9
AN:
1098236
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31
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2
AN XY:
363592
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GnomAD4 genome ? Cov.: 24
GnomAD4 genome
?
Cov.:
24
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
X-linked myopathy with postural muscle atrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Apr 04, 2023 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
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