rs371828469
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_001134363.3(RBM20):c.3268A>T(p.Ile1090Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000213 in 1,551,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict 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. I1090N) has been classified as Uncertain significance.
Frequency
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.3268A>T | p.Ile1090Phe | missense_variant | 11/14 | ENST00000369519.4 | |
RBM20 | XM_017016103.3 | c.3103A>T | p.Ile1035Phe | missense_variant | 11/14 | ||
RBM20 | XM_017016104.3 | c.2884A>T | p.Ile962Phe | missense_variant | 11/14 | ||
RBM20 | XM_047425116.1 | c.2884A>T | p.Ile962Phe | missense_variant | 11/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RBM20 | ENST00000369519.4 | c.3268A>T | p.Ile1090Phe | missense_variant | 11/14 | 1 | NM_001134363.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000319 AC: 5AN: 156500Hom.: 0 AF XY: 0.0000241 AC XY: 2AN XY: 82952
GnomAD4 exome AF: 0.0000157 AC: 22AN: 1399404Hom.: 0 Cov.: 33 AF XY: 0.0000145 AC XY: 10AN XY: 690208
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74462
ClinVar
Submissions by phenotype
Dilated cardiomyopathy 1DD Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 11, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 27, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 12, 2023 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 05, 2022 | The p.I1090F variant (also known as c.3268A>T), located in coding exon 11 of the RBM20 gene, results from an A to T substitution at nucleotide position 3268. The isoleucine at codon 1090 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at