rs3744903
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001281740.3(FHOD3):c.3477C>T(p.Asn1159Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.338 in 1,613,170 control chromosomes in the GnomAD database, including 94,866 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.30 ( 7308 hom., cov: 32)
Exomes 𝑓: 0.34 ( 87558 hom. )
Consequence
FHOD3
NM_001281740.3 synonymous
NM_001281740.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.500
Genes affected
FHOD3 (HGNC:26178): (formin homology 2 domain containing 3) The protein encoded by this gene is a member of the diaphanous-related formins (DRF), and contains multiple domains, including GBD (GTPase-binding domain), DID (diaphanous inhibitory domain), FH1 (formin homology 1), FH2 (formin homology 2), and DAD (diaphanous auto-regulatory domain) domains. This protein is thought to play a role in actin filament polymerization in cardiomyocytes. Mutations in this gene have been associated with dilated cardiomyopathy (DCM), characterized by dilation of the ventricular chamber, leading to impairment of systolic pump function and subsequent heart failure. Increased levels of the protein encoded by this gene have been observed in individuals with hypertrophic cardiomyopathy (HCM). Alternative splicing results in multiple transcript variants encoding different isoforms. A muscle-specific isoform has been shown to possess a casein kinase 2 (CK2) phosphorylation site at the C-terminal end of the FH2 domain. Phosphorylation of this site alters its interaction with sequestosome 1 (SQSTM1), and targets this isoform to myofibrils, while other isoforms form cytoplasmic aggregates. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 18-36730705-C-T is Benign according to our data. Variant chr18-36730705-C-T is described in ClinVar as [Benign]. Clinvar id is 1239394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.5 with no splicing effect.
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FHOD3 | NM_001281740.3 | c.3477C>T | p.Asn1159Asn | synonymous_variant | 20/29 | ENST00000590592.6 | NP_001268669.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FHOD3 | ENST00000590592.6 | c.3477C>T | p.Asn1159Asn | synonymous_variant | 20/29 | 1 | NM_001281740.3 | ENSP00000466937.1 |
Frequencies
GnomAD3 genomes AF: 0.299 AC: 45490AN: 151946Hom.: 7298 Cov.: 32
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GnomAD3 exomes AF: 0.350 AC: 87893AN: 251090Hom.: 16432 AF XY: 0.353 AC XY: 47939AN XY: 135714
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GnomAD4 exome AF: 0.342 AC: 499219AN: 1461106Hom.: 87558 Cov.: 35 AF XY: 0.345 AC XY: 250445AN XY: 726866
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GnomAD4 genome AF: 0.299 AC: 45510AN: 152064Hom.: 7308 Cov.: 32 AF XY: 0.302 AC XY: 22426AN XY: 74302
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 06, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at