rs201917318
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP2PP3BS2
The NM_001458.5(FLNC):c.7108G>A(p.Gly2370Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G2370G) has been classified as Benign.
Frequency
Consequence
NM_001458.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.7108G>A | p.Gly2370Ser | missense_variant | 42/48 | ENST00000325888.13 | |
FLNC-AS1 | NR_149055.1 | n.103-1488C>T | intron_variant, non_coding_transcript_variant | ||||
FLNC | NM_001127487.2 | c.7009G>A | p.Gly2337Ser | missense_variant | 41/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.7108G>A | p.Gly2370Ser | missense_variant | 42/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.7009G>A | p.Gly2337Ser | missense_variant | 41/47 | 1 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.103-1488C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249458Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135358
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461776Hom.: 0 Cov.: 33 AF XY: 0.0000248 AC XY: 18AN XY: 727188
GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Apr 03, 2023 | BS2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 05, 2020 | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#432546; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 03, 2021 | - - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 09, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2022 | The p.G2370S variant (also known as c.7108G>A), located in coding exon 42 of the FLNC gene, results from a G to A substitution at nucleotide position 7108. The glycine at codon 2370 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. 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 | Jan 26, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at