chr11-47333231-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_000256.3(MYBPC3):c.3293G>T(p.Trp1098Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W1098C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000256.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.3293G>T | p.Trp1098Leu | missense_variant | 30/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.3293G>T | p.Trp1098Leu | missense_variant | 30/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.3293G>T | p.Trp1098Leu | missense_variant | 29/34 | 5 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1443262Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 716040
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 06, 2012 | This variant is denoted p.Trp1098Leu (TGG>TTG): c.3293 G>T in exon 30 of the MYBPC3 gene (NM_000256.3). The Trp1098Leu variant in the MYBPC3 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Trp1098Leu results in a conservative amino acid substitution of one non-polar residue for another at a position that is conserved across species. In silico analysis predicts Trp1098Leu is benign to the protein structure/function. However, missense mutations affecting nearby residues (Glu1096Lys, Thr1109Ile) have been reported in association with HCM, supporting the functional importance of this region of the protein. Furthermore, the NHLBI ESP Exome Variant Server reports Trp1098Leu was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. With the clinical and molecular information available at this time, we cannot definitively determine if Trp1098Leu is a disease-causing mutation or a rare benign variant. The variant is found in HCM panel(s). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at