10-110781139-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001134363.3(RBM20):c.530C>T(p.Thr177Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000251 in 1,551,724 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001134363.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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RBM20 | NM_001134363.3 | c.530C>T | p.Thr177Ile | missense_variant | Exon 2 of 14 | ENST00000369519.4 | NP_001127835.2 | |
RBM20 | XM_017016103.3 | c.365C>T | p.Thr122Ile | missense_variant | Exon 2 of 14 | XP_016871592.1 | ||
RBM20 | XM_017016104.3 | c.146C>T | p.Thr49Ile | missense_variant | Exon 2 of 14 | XP_016871593.1 | ||
RBM20 | XM_047425116.1 | c.146C>T | p.Thr49Ile | missense_variant | Exon 2 of 14 | XP_047281072.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00124 AC: 189AN: 152212Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000333 AC: 52AN: 156040Hom.: 0 AF XY: 0.000278 AC XY: 23AN XY: 82748
GnomAD4 exome AF: 0.000144 AC: 201AN: 1399394Hom.: 1 Cov.: 32 AF XY: 0.000128 AC XY: 88AN XY: 690196
GnomAD4 genome AF: 0.00124 AC: 189AN: 152330Hom.: 1 Cov.: 32 AF XY: 0.00128 AC XY: 95AN XY: 74490
ClinVar
Submissions by phenotype
not specified Benign:4
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Thr177Ile in exon 2 of RBM20: This variant is not expected to have clinical sign ificance because it has been identified in 1.7% (3/176) of Yoruba (African) chro mosomes by the 1000 Genomes project (dbSNP rs183130427). Thr177Ile in exon 2 of RBM20 (rs183130427; allele frequency = 1.7%, 3/176) -
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not provided Uncertain:1Benign:2
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Dilated cardiomyopathy 1DD Uncertain:1Benign:1
RBM20 NM_001134363.2 exon 2 p.Thr177Ile (c.530C>T): This variant has not been reported in the literature and is present in 0.5% (84/16618) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/10-112540897-C-T). This variant is also present in ClinVar, with several labs classifying this variant as benign or likely benign (Variation ID:44024). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease, but requires further evidence. Therefore this variant is classified as likely benign. -
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Cardiomyopathy Benign:2
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Cardiovascular phenotype 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at