X-154367698-G-A
Variant summary
Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001110556.2(FLNA):c.663C>T(p.Pro221Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00435 in 1,209,832 control chromosomes in the GnomAD database, including 154 homozygotes. There are 1,500 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P221P) has been classified as Likely benign.
Frequency
Consequence
NM_001110556.2 synonymous
Scores
Clinical Significance
Conservation
Publications
- periventricular nodular heterotopiaInheritance: AD, XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- frontometaphyseal dysplasia 1Inheritance: XL Classification: DEFINITIVE Submitted by: G2P
- genetic developmental and epileptic encephalopathyInheritance: XL Classification: DEFINITIVE Submitted by: G2P
- heterotopia, periventricular, X-linked dominantInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Illumina
- intestinal pseudoobstruction, neuronal, chronic idiopathic, X-linkedInheritance: XL Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
- Melnick-Needles syndromeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
- otopalatodigital syndrome type 2Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)
- terminal osseous dysplasia-pigmentary defects syndromeInheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
- cardiac valvular dysplasia, X-linkedInheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- frontometaphyseal dysplasiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- congenital short bowel syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- otopalatodigital syndrome type 1Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
- X-linked Ehlers-Danlos syndromeInheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
- familial thoracic aortic aneurysm and aortic dissectionInheritance: XL Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Benign. The variant received -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLNA | NM_001110556.2 | c.663C>T | p.Pro221Pro | synonymous_variant | Exon 4 of 48 | ENST00000369850.10 | NP_001104026.1 | |
FLNA | NM_001456.4 | c.663C>T | p.Pro221Pro | synonymous_variant | Exon 4 of 47 | NP_001447.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00509 AC: 572AN: 112354Hom.: 11 Cov.: 25 show subpopulations
GnomAD2 exomes AF: 0.0157 AC: 2842AN: 181390 AF XY: 0.0110 show subpopulations
GnomAD4 exome AF: 0.00426 AC: 4677AN: 1097423Hom.: 142 Cov.: 33 AF XY: 0.00362 AC XY: 1314AN XY: 363255 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00517 AC: 581AN: 112409Hom.: 12 Cov.: 25 AF XY: 0.00538 AC XY: 186AN XY: 34591 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not specified Benign:7
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BS1;BP6;BP7 -
Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
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. -
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not provided Benign:2
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Familial thoracic aortic aneurysm and aortic dissection Benign:1
This alteration is classified as 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at