rs12810816

Positions:

• chr12-56159176-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000550697.6(MYL6):​c.32-411T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 286,098 control chromosomes in the GnomAD database, including 1,689 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (847 hom., cov: 32)
  • Exomes 𝑓: 0.10 (842 hom.)
• Consequence: MYL6 ENST00000550697.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL6	NM_021019.5	c.32-411T>G		intron_variant		ENST00000550697.6	NP_066299.2
MYL6	NM_079423.4	c.32-411T>G		intron_variant			NP_524147.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL6	ENST00000550697.6	c.32-411T>G		intron_variant		1	NM_021019.5	ENSP00000446955

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15624 AN: 152130 Hom.: 847 Cov.: 32

Gnomad AFR AF: 0.0918

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0845

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0778

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.118

Gnomad OTH AF: 0.0866

GnomAD4 exome AF: 0.102 AC: 13636 AN: 133850 Hom.: 842 Cov.: 4 AF XY: 0.100 AC XY: 7119 AN XY: 70958

Gnomad4 AFR exome AF: 0.0922

Gnomad4 AMR exome AF: 0.0666

Gnomad4 ASJ exome AF: 0.130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0782

Gnomad4 FIN exome AF: 0.117

Gnomad4 NFE exome AF: 0.115

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.103 AC: 15633 AN: 152248 Hom.: 847 Cov.: 32 AF XY: 0.102 AC XY: 7621 AN XY: 74420

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.0844

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0781

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.118

Gnomad4 OTH AF: 0.0857

Alfa AF: 0.115 Hom.: 1330

Bravo AF: 0.0990

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.68

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: rs12810816; hg19: chr12-56552960;