rs782774182
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4BP6BS2
The NM_001110556.2(FLNA):āc.4082A>Gā(p.His1361Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,209,424 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 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. H1361Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001110556.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.4082A>G | p.His1361Arg | missense_variant | 24/48 | ENST00000369850.10 | |
FLNA | NM_001456.4 | c.4082A>G | p.His1361Arg | missense_variant | 24/47 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLNA | ENST00000369850.10 | c.4082A>G | p.His1361Arg | missense_variant | 24/48 | 1 | NM_001110556.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000894 AC: 1AN: 111864Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34090
GnomAD3 exomes AF: 0.0000940 AC: 17AN: 180916Hom.: 0 AF XY: 0.000134 AC XY: 9AN XY: 67180
GnomAD4 exome AF: 0.0000128 AC: 14AN: 1097560Hom.: 0 Cov.: 34 AF XY: 0.0000220 AC XY: 8AN XY: 363194
GnomAD4 genome ? AF: 0.00000894 AC: 1AN: 111864Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 34090
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 05, 2014 | The H1361R variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The H1361R variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved among mammals. However, the H1361R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Additionally, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. This variant was found in TAAD - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 24, 2023 | 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. - |
Melnick-Needles syndrome;C0265293:Frontometaphyseal dysplasia;C1844696:Oto-palato-digital syndrome, type II;C1848213:Heterotopia, periventricular, X-linked dominant Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 26, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at