2-210293763-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_079420.3(MYL1):c.516G>A(p.Met172Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
MYL1
NM_079420.3 missense
NM_079420.3 missense
Scores
1
5
11
Clinical Significance
Conservation
PhyloP100: 2.77
Genes affected
MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.36730236).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL1 | NM_079420.3 | c.516G>A | p.Met172Ile | missense_variant | 5/7 | ENST00000352451.4 | |
MYL1 | NM_079422.3 | c.384G>A | p.Met128Ile | missense_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL1 | ENST00000352451.4 | c.516G>A | p.Met172Ile | missense_variant | 5/7 | 1 | NM_079420.3 | ||
MYL1 | ENST00000341685.8 | c.384G>A | p.Met128Ile | missense_variant | 5/7 | 1 | P1 | ||
MYL1 | ENST00000484290.1 | n.647G>A | non_coding_transcript_exon_variant | 6/6 | 5 | ||||
MYL1 | ENST00000496436.5 | n.619G>A | non_coding_transcript_exon_variant | 5/6 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 20, 2021 | The c.516G>A (p.M172I) alteration is located in exon 5 (coding exon 5) of the MYL1 gene. This alteration results from a G to A substitution at nucleotide position 516, causing the methionine (M) at amino acid position 172 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Benign
T;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
0.54
.;Loss of catalytic residue at V168 (P = 0.0209);
MVP
MPC
0.085
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at