rs529967791

Variant names:

• chr12-56155460-A-G
• rs529967791
• NM_002475.5:c.388A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-56155460-A-G
• chr12-56155460-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002475.5(MYL6B):​c.388A>G​(p.Met130Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYL6B NM_002475.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.31

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL6B	NM_002475.5	c.388A>G	p.Met130Val	missense_variant	Exon 5 of 8	ENST00000695999.1	NP_002466.1
MYL6B	NM_001199629.2	c.388A>G	p.Met130Val	missense_variant	Exon 5 of 8		NP_001186558.1
MYL6B-AS1	NR_186043.1	n.355+2174T>C		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL6B	ENST00000695999.1	c.388A>G	p.Met130Val	missense_variant	Exon 5 of 8		NM_002475.5	ENSP00000512320.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.36
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.38	T;T;.
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	.;T;T
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.77	D;D;D
MetaSVM	Uncertain	0.51	D
MutationAssessor	Uncertain	2.9	M;M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Pathogenic	0.90
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.060	T;T;D
Polyphen		0.98	D;D;.
Vest4		0.63
MutPred		0.58		Gain of catalytic residue at F127 (P = 0.059);Gain of catalytic residue at F127 (P = 0.059);Gain of catalytic residue at F127 (P = 0.059);
MVP		0.87
MPC		0.58
ClinPred		0.96	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.75
gMVP		0.69

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: rs529967791; hg19: chr12-56549244;