10-110821641-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2
The NM_001134363.3(RBM20):c.3022C>T(p.Arg1008Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,551,614 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1008P) 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 -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RBM20 | NM_001134363.3 | c.3022C>T | p.Arg1008Trp | missense_variant | Exon 11 of 14 | ENST00000369519.4 | NP_001127835.2 | |
RBM20 | XM_017016103.3 | c.2857C>T | p.Arg953Trp | missense_variant | Exon 11 of 14 | XP_016871592.1 | ||
RBM20 | XM_017016104.3 | c.2638C>T | p.Arg880Trp | missense_variant | Exon 11 of 14 | XP_016871593.1 | ||
RBM20 | XM_047425116.1 | c.2638C>T | p.Arg880Trp | missense_variant | Exon 11 of 14 | XP_047281072.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000128 AC: 2AN: 156560Hom.: 0 AF XY: 0.0000121 AC XY: 1AN XY: 82928
GnomAD4 exome AF: 0.0000136 AC: 19AN: 1399420Hom.: 0 Cov.: 33 AF XY: 0.0000145 AC XY: 10AN XY: 690200
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152194Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant classified as Uncertain Significance - Favor Benign. The Arg1008Trp vari ant (RBM20) has not been reported in the literature nor previously identified by our laboratory. Arginine (Arg) at position 1008 is not conserved in mammals and computational analyses (AlignGVGD and PolyPhen2) suggest that a change to trypt ophan (Trp) may impact the protein, though this information is not predictive en ough to rule out pathogenicity. While the lack of conservation in mammals sugges ts that the Arg1008Trp variant may be benign, additional information is needed t o fully assess its clinical significance. -
Dilated cardiomyopathy 1DD Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at