rs374743518
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_001458.5(FLNC):c.5889G>A(p.Thr1963=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,613,308 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T1963T) has been classified as Likely benign.
Frequency
Consequence
NM_001458.5 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNC | NM_001458.5 | c.5889G>A | p.Thr1963= | synonymous_variant | 36/48 | ENST00000325888.13 | |
FLNC-AS1 | NR_149055.1 | n.215+648C>T | intron_variant, non_coding_transcript_variant | ||||
FLNC | NM_001127487.2 | c.5790G>A | p.Thr1930= | synonymous_variant | 35/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNC | ENST00000325888.13 | c.5889G>A | p.Thr1963= | synonymous_variant | 36/48 | 1 | NM_001458.5 | P3 | |
FLNC | ENST00000346177.6 | c.5790G>A | p.Thr1930= | synonymous_variant | 35/47 | 1 | A1 | ||
FLNC-AS1 | ENST00000469965.1 | n.215+648C>T | intron_variant, non_coding_transcript_variant | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000223 AC: 34AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000438 AC: 109AN: 248658Hom.: 0 AF XY: 0.000414 AC XY: 56AN XY: 135206
GnomAD4 exome AF: 0.000176 AC: 257AN: 1460996Hom.: 0 Cov.: 33 AF XY: 0.000191 AC XY: 139AN XY: 726806
GnomAD4 genome ? AF: 0.000223 AC: 34AN: 152312Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74482
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | FLNC: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 24, 2021 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 16, 2019 | 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. - |
Myofibrillar myopathy 5;C3279722:Distal myopathy with posterior leg and anterior hand involvement;C4310749:Hypertrophic cardiomyopathy 26;CN239310:Dilated Cardiomyopathy, Dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at