12-56158687-G-A

Position:

• chr12-56158687-G-A

Variant summary

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

The NM_021019.5(MYL6):​c.7G>A​(p.Asp3Asn) variant causes a missense change. 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: 31)
• Consequence: MYL6 NM_021019.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36485124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL6	NM_021019.5	c.7G>A	p.Asp3Asn	missense_variant	2/7	ENST00000550697.6	NP_066299.2
MYL6	NM_079423.4	c.7G>A	p.Asp3Asn	missense_variant	2/6		NP_524147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL6	ENST00000550697.6	c.7G>A	p.Asp3Asn	missense_variant	2/7	1	NM_021019.5	ENSP00000446955.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Oct 05, 2022

The c.7G>A (p.D3N) alteration is located in exon 2 (coding exon 2) of the MYL6 gene. This alteration results from a G to A substitution at nucleotide position 7, causing the aspartic acid (D) at amino acid position 3 to be replaced by an asparagine (N). 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	Uncertain	0.37
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;T;T;T;.;.;.;.;T;.;T;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.58	.;T;D;D;T;D;D;D;D;D;D;D
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.36	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.020	D
MutationAssessor	Benign	-0.070	N;.;.;.;.;.;N;.;.;.;.;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.0	N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Uncertain	0.34
Sift	Benign	0.17	T;T;T;T;D;T;T;T;T;T;T;T
Sift4G	Benign	0.20	T;D;T;T;D;T;T;T;T;T;T;T
Polyphen		0.17	B;.;.;.;.;D;B;.;B;.;.;B
Vest4		0.36
MutPred		0.34		.;.;.;.;Loss of disorder (P = 0.1319);Loss of disorder (P = 0.1319);.;.;.;.;.;.;
MVP		0.89
MPC		0.44
ClinPred		0.90	D
GERP RS		4.5
Varity_R		0.34
gMVP		0.17

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr12-56552471;