2-210293763-C-T

Position:

• chr2-210293763-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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]

ACMG classification

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

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000370 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Benign	-0.013	T
BayesDel_noAF	Benign	-0.26
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	.;T
Eigen	Benign	-0.022
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	1.2	.;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.39
Sift	Benign	0.055	T;D
Sift4G	Benign	0.78	T;T
Polyphen		0.0020	B;B
Vest4		0.51
MutPred		0.54		.;Loss of catalytic residue at V168 (P = 0.0209);
MVP		0.85
MPC		0.085
ClinPred		0.82	D
GERP RS		5.9
Varity_R		0.30
gMVP		0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1690121763; hg19: chr2-211158487;