rs12810816

Variant names:

• chr12-56159176-T-G
• rs12810816
• NM_021019.5:c.32-411T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021019.5(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 NM_021019.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021019.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL6	NM_021019.5	MANE Select	c.32-411T>G		intron	N/A	NP_066299.2
	MYL6	NM_079423.4		c.32-411T>G		intron	N/A	NP_524147.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL6	ENST00000550697.6	TSL:1 MANE Select	c.32-411T>G		intron	N/A	ENSP00000446955.2
	MYL6	ENST00000547649.5	TSL:1	c.32-411T>G		intron	N/A	ENSP00000446714.1
	MYL6	ENST00000546630.1	TSL:1	n.340-411T>G		intron	N/A

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

African (AFR) AF: 0.0922 AC: 361 AN: 3914

American (AMR) AF: 0.0666 AC: 346 AN: 5198

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 489 AN: 3752

East Asian (EAS) AF: 0.00 AC: 0 AN: 6538

South Asian (SAS) AF: 0.0782 AC: 1312 AN: 16772

European-Finnish (FIN) AF: 0.117 AC: 656 AN: 5596

Middle Eastern (MID) AF: 0.0719 AC: 41 AN: 570

European-Non Finnish (NFE) AF: 0.115 AC: 9628 AN: 84048

Other (OTH) AF: 0.108 AC: 803 AN: 7462

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

African (AFR) AF: 0.0918 AC: 3814 AN: 41546

American (AMR) AF: 0.0844 AC: 1291 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 445 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0781 AC: 377 AN: 4830

European-Finnish (FIN) AF: 0.124 AC: 1312 AN: 10592

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.118 AC: 8045 AN: 68004

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

Alfa AF: 0.112 Hom.: 1792

Bravo AF: 0.0990

Asia WGS AF: 0.0290 AC: 101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.68
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12810816; hg19: chr12-56552960;