12-56155460-ATG-CTT

Variant names:

• chr12-56155460-ATG-CTT
• NM_002475.5:c.388_390delATGinsCTT
• MYL6B p.Met130Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_002475.5(MYL6B):​c.388_390delATGinsCTT​(p.Met130Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL6B NM_002475.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.31
• Publications: 0 publications found

Genes affected

MYL6B (HGNC:29823): (myosin light chain 6B) 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 both slow-twitch skeletal muscle and in nonmuscle tissue. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

MYL6B-AS1 (HGNC:55472): (MYL6B antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002475.5. 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
	MYL6B	NM_002475.5	MANE Select	c.388_390delATGinsCTT	p.Met130Leu	missense	N/A	NP_002466.1	P14649
	MYL6B	NM_001199629.2		c.388_390delATGinsCTT	p.Met130Leu	missense	N/A	NP_001186558.1	P14649
	MYL6B-AS1	NR_186043.1		n.355+2172_355+2174delCATinsAAG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL6B	ENST00000695999.1	MANE Select	c.388_390delATGinsCTT	p.Met130Leu	missense	N/A	ENSP00000512320.1	P14649
	MYL6B	ENST00000550443.5	TSL:1	c.388_390delATGinsCTT	p.Met130Leu	missense	N/A	ENSP00000446643.1	P14649
	MYL6B	ENST00000696001.1		c.415_417delATGinsCTT	p.Met139Leu	missense	N/A	ENSP00000512322.1	A0A8Q3SIC5

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-56549244;