7-128830656-T-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001458.5(FLNC):c.19T>G(p.Tyr7Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,612,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. Y7Y) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.19T>G | p.Tyr7Asp | missense_variant | 1/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.19T>G | p.Tyr7Asp | missense_variant | 1/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.19T>G | p.Tyr7Asp | missense_variant | 1/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.19T>G | p.Tyr7Asp | missense_variant | 1/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152080Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460082Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 726336
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152080Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74274
ClinVar
Submissions by phenotype
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 09, 2024 | The p.Y7D variant (also known as c.19T>G), located in coding exon 1 of the FLNC gene, results from a T to G substitution at nucleotide position 19. The tyrosine at codon 7 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 848024). This variant has not been reported in the literature in individuals affected with FLNC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 7 of the FLNC protein (p.Tyr7Asp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at