12-56159650-G-A

Position:

• chr12-56159650-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021019.5(MYL6):​c.95G>A​(p.Cys32Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL6 NM_021019.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.54

Genes affected

MYL6 (HGNC:7587): (myosin light chain 6) 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 that is expressed in smooth muscle and non-muscle tissues. Genomic sequences representing several pseudogenes have been described and two transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL6 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL6	NM_021019.5	c.95G>A	p.Cys32Tyr	missense_variant	3/7	ENST00000550697.6	NP_066299.2
MYL6	NM_079423.4	c.95G>A	p.Cys32Tyr	missense_variant	3/6		NP_524147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL6	ENST00000550697.6	c.95G>A	p.Cys32Tyr	missense_variant	3/7	1	NM_021019.5	ENSP00000446955.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Mar 02, 2023

The c.95G>A (p.C32Y) alteration is located in exon 3 (coding exon 3) of the MYL6 gene. This alteration results from a G to A substitution at nucleotide position 95, causing the cysteine (C) at amino acid position 32 to be replaced by a tyrosine (Y). 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	0.99
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	29
DANN	Benign	0.97
DEOGEN2	Uncertain	0.43	T;T;T;.;.;.;T;.;T
Eigen	Benign	0.017
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	.;T;T;T;T;T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.71	D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	0.20	N;.;.;.;N;.;.;.;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-6.2	D;D;D;D;D;D;D;D;D
REVEL	Uncertain	0.60
Sift	Uncertain	0.028	D;D;D;D;D;D;D;D;D
Sift4G	Uncertain	0.038	D;D;D;D;D;D;D;T;D
Polyphen		0.18	B;.;.;P;B;.;B;.;B
Vest4		0.86
MutPred		0.54		.;.;.;Gain of phosphorylation at C125 (P = 0.0516);.;.;.;.;.;
MVP		0.98
MPC		0.86
ClinPred		0.82	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.74
gMVP		0.76

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-56553434;