NM_000256.3:c.1494C>G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000256.3(MYBPC3):c.1494C>G(p.Thr498Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,904 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 Likely benign (★★).
Frequency
Consequence
NM_000256.3 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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MYBPC3 | ENST00000545968.6 | c.1494C>G | p.Thr498Thr | synonymous_variant | Exon 17 of 35 | 5 | NM_000256.3 | ENSP00000442795.1 | ||
MYBPC3 | ENST00000399249.6 | c.1494C>G | p.Thr498Thr | synonymous_variant | Exon 16 of 34 | 5 | ENSP00000382193.2 | |||
MYBPC3 | ENST00000544791.1 | n.1494C>G | non_coding_transcript_exon_variant | Exon 17 of 27 | 5 | ENSP00000444259.1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000562 AC: 14AN: 249244Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135216
GnomAD4 exome AF: 0.0000383 AC: 56AN: 1461696Hom.: 0 Cov.: 31 AF XY: 0.0000385 AC XY: 28AN XY: 727134
GnomAD4 genome AF: 0.0000591 AC: 9AN: 152208Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74364
ClinVar
Submissions by phenotype
not provided Benign:5
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MYBPC3: BP4, BP7 -
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Cardiomyopathy Benign:2
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not specified Benign:1
Thr498Thr in exon 17 of MYBPC3: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. Thr498Thr in exon 17 of MYBPC3 (allele fre quency = n/a) -
Hypertrophic cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely 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