rs200111933
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_002465.4(MYBPC1):āc.1946T>Cā(p.Val649Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000185 in 1,613,518 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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_002465.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYBPC1 | NM_002465.4 | c.1946T>C | p.Val649Ala | missense_variant | 20/32 | ENST00000361466.7 | |
LOC124902996 | XR_007063422.1 | n.85-781A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYBPC1 | ENST00000361466.7 | c.1946T>C | p.Val649Ala | missense_variant | 20/32 | 1 | NM_002465.4 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152172Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000111 AC: 28AN: 251286Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135802
GnomAD4 exome AF: 0.000189 AC: 276AN: 1461346Hom.: 1 Cov.: 30 AF XY: 0.000172 AC XY: 125AN XY: 726994
GnomAD4 genome ? AF: 0.000145 AC: 22AN: 152172Hom.: 0 Cov.: 31 AF XY: 0.000108 AC XY: 8AN XY: 74360
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | MYBPC1: BP4 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 28, 2022 | The c.1946T>C (p.V649A) alteration is located in exon 20 (coding exon 20) of the MYBPC1 gene. This alteration results from a T to C substitution at nucleotide position 1946, causing the valine (V) at amino acid position 649 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 06, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at