chr11-47349911-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000256.3(MYBPC3):āc.517A>Gā(p.Thr173Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000438 in 1,598,858 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T173I) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC3 | NM_000256.3 | c.517A>G | p.Thr173Ala | missense_variant | 5/35 | ENST00000545968.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC3 | ENST00000545968.6 | c.517A>G | p.Thr173Ala | missense_variant | 5/35 | 5 | NM_000256.3 | P4 | |
MYBPC3 | ENST00000399249.6 | c.517A>G | p.Thr173Ala | missense_variant | 5/34 | 5 | A2 | ||
MYBPC3 | ENST00000544791.1 | c.517A>G | p.Thr173Ala | missense_variant, NMD_transcript_variant | 5/27 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000685 AC: 1AN: 146034Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000446 AC: 1AN: 224276Hom.: 0 AF XY: 0.00000818 AC XY: 1AN XY: 122196
GnomAD4 exome AF: 0.00000413 AC: 6AN: 1452824Hom.: 0 Cov.: 31 AF XY: 0.00000277 AC XY: 2AN XY: 721904
GnomAD4 genome AF: 0.00000685 AC: 1AN: 146034Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 70936
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Oct 23, 2023 | This missense variant replaces threonine with alanine at codon 173 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 28138913) and in an individual suspected to be affected with hypertrophic cardiomyopathy (PMID: 33673806). This variant has been identified in 1/224276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 08, 2022 | This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 173 of the MYBPC3 protein (p.Thr173Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 28138913, 33673806). ClinVar contains an entry for this variant (Variation ID: 179848). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 11, 2019 | proposed classification - variant undergoing re-assessment, contact laboratory - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | May 12, 2023 | This missense variant replaces threonine with alanine at codon 173 of the MYBPC3 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 28138913) and in an individual suspected to be affected with hypertrophic cardiomyopathy (PMID: 33673806). This variant has been identified in 1/224276 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at