rs753945728
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_001458.5(FLNC):c.5000C>T(p.Thr1667Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1667R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.5000C>T | p.Thr1667Met | missense_variant | 30/48 | ENST00000325888.13 | |
FLNC | NM_001127487.2 | c.5000C>T | p.Thr1667Met | missense_variant | 30/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.5000C>T | p.Thr1667Met | missense_variant | 30/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.5000C>T | p.Thr1667Met | missense_variant | 30/47 | 1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249304Hom.: 1 AF XY: 0.0000370 AC XY: 5AN XY: 135294
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461766Hom.: 0 Cov.: 36 AF XY: 0.0000220 AC XY: 16AN XY: 727184
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74372
ClinVar
Submissions by phenotype
Myofibrillar myopathy 5 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Human Genetics Bochum, Ruhr University Bochum | Jul 28, 2023 | ACMG criteria used to clasify this variant: PP3_MOD - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 2022 | The p.T1667M variant (also known as c.5000C>T), located in coding exon 30 of the FLNC gene, results from a C to T substitution at nucleotide position 5000. The threonine at codon 1667 is replaced by methionine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 25, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at