12-110911131-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000432.4(MYL2):c.447C>T(p.Asn149Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,464 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_000432.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYL2 | NM_000432.4 | c.447C>T | p.Asn149Asn | synonymous_variant | Exon 7 of 7 | ENST00000228841.15 | NP_000423.2 | |
MYL2 | NM_001406745.1 | c.405C>T | p.Asn135Asn | synonymous_variant | Exon 6 of 6 | NP_001393674.1 | ||
MYL2 | NM_001406916.1 | c.390C>T | p.Asn130Asn | synonymous_variant | Exon 7 of 7 | NP_001393845.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYL2 | ENST00000228841.15 | c.447C>T | p.Asn149Asn | synonymous_variant | Exon 7 of 7 | 1 | NM_000432.4 | ENSP00000228841.8 | ||
MYL2 | ENST00000548438.1 | c.405C>T | p.Asn135Asn | synonymous_variant | Exon 6 of 6 | 3 | ENSP00000447154.1 | |||
MYL2 | ENST00000663220.1 | c.390C>T | p.Asn130Asn | synonymous_variant | Exon 7 of 7 | ENSP00000499568.1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151948Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461516Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727044
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151948Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74196
ClinVar
Submissions by phenotype
not specified Benign:1
Asn149Asn in exon 7 of MYL2: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. Asn149Asn in exon 7 of MYL2 (allele frequency = n/a) -
Hypertrophic cardiomyopathy 10 Benign:1
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Cardiomyopathy Benign:1
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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