rs1259220084

Variant names:

• chr2-210293791-A-C
• rs1259220084
• NM_079420.3:c.488T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-210293791-A-C
• chr2-210293791-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_079420.3(MYL1):​c.488T>G​(p.Met163Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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 P:1 U:1
• Conservation: PhyloP100: 9.32
• Publications: 2 publications found

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]

MYL1 Gene-Disease associations (from GenCC):

• congenital myopathy with reduced type 2 muscle fibers

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital myopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000279317 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.843

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_079420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	NM_079420.3	MANE Select	c.488T>G	p.Met163Arg	missense	Exon 5 of 7	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.356T>G	p.Met119Arg	missense	Exon 5 of 7	NP_524146.1	P05976-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	ENST00000352451.4	TSL:1 MANE Select	c.488T>G	p.Met163Arg	missense	Exon 5 of 7	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.356T>G	p.Met119Arg	missense	Exon 5 of 7	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.452T>G	p.Met151Arg	missense	Exon 5 of 7	ENSP00000627437.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
1	1	-	Congenital myopathy with reduced type 2 muscle fibers (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.97
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.71	D
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.95
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.19	D
MetaRNN	Pathogenic	0.84	D
MetaSVM	Uncertain	0.75	D
MutationAssessor	Pathogenic	3.9	H
PhyloP100		9.3
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.5	D
REVEL	Pathogenic	0.87
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.97	D
Vest4		0.92
MutPred		0.54		Gain of methylation at K162 (P = 0.0264)
MVP		0.93
MPC		0.53
ClinPred		1.0	D
GERP RS		5.9
Varity_R		0.96
gMVP		0.96
Mutation Taster		=0/100	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1259220084; hg19: chr2-211158515;