rs746027670

Variant names:

• chr4-119136544-A-C
• rs746027670
• NM_016599.5:c.19A>C

Your query was ambiguous. Multiple possible variants found:

• chr4-119136544-A-C
• chr4-119136544-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016599.5(MYOZ2):​c.19A>C​(p.Met7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOZ2 NM_016599.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381

Genes affected

MYOZ2 (HGNC:1330): (myozenin 2) The protein encoded by this gene belongs to a family of sarcomeric proteins that bind to calcineurin, a phosphatase involved in calcium-dependent signal transduction in diverse cell types. These family members tether calcineurin to alpha-actinin at the z-line of the sarcomere of cardiac and skeletal muscle cells, and thus they are important for calcineurin signaling. Mutations in this gene cause cardiomyopathy familial hypertrophic type 16, a hereditary heart disorder. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13726625).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOZ2	NM_016599.5	c.19A>C	p.Met7Leu	missense_variant	Exon 2 of 6	ENST00000307128.6	NP_057683.1
MYOZ2	XM_006714234.5	c.19A>C	p.Met7Leu	missense_variant	Exon 2 of 6		XP_006714297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOZ2	ENST00000307128.6	c.19A>C	p.Met7Leu	missense_variant	Exon 2 of 6	1	NM_016599.5	ENSP00000306997.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	13
DANN	Benign	0.72
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.40	N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.088
Sift	Benign	0.60	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.34
MutPred		0.60		Loss of methylation at K9 (P = 0.0719);
MVP		0.47
MPC		0.16
ClinPred		0.046	T
GERP RS		-2.0
Varity_R		0.075
gMVP		0.19

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: rs746027670; hg19: chr4-120057699;