rs397517473
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The ENST00000375985.5(MYLK2):c.277C>A(p.Pro93Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000548 in 1,460,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P93P) has been classified as Likely benign.
Frequency
Consequence
ENST00000375985.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYLK2 | NM_033118.4 | c.277C>A | p.Pro93Thr | missense_variant | 3/13 | ENST00000375985.5 | NP_149109.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYLK2 | ENST00000375985.5 | c.277C>A | p.Pro93Thr | missense_variant | 3/13 | 1 | NM_033118.4 | ENSP00000365152 | P1 | |
MYLK2 | ENST00000375994.6 | c.277C>A | p.Pro93Thr | missense_variant | 2/12 | 1 | ENSP00000365162 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000203 AC: 5AN: 246290Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134128
GnomAD4 exome AF: 0.00000548 AC: 8AN: 1460396Hom.: 0 Cov.: 32 AF XY: 0.00000688 AC XY: 5AN XY: 726470
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 11, 2012 | Variant classified as Uncertain Significance - Favor Benign. The Pro93Thr varian t in MYLK2 has not been reported in the literature nor previously identified by our laboratory. Proline (Pro) at position 93 is not conserved in mammals, despit e high nearby amino acid conservation. Computational analyses (biochemical amino acid properties, AlignGVGD, and SIFT) suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathog enicity. Although the lack of conservation and computational tools suggest that the Pro93Thr variant may be benign, additional studies are needed to fully asses s its clinical significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at