NM_001122853.3:c.712G>A

Variant names:

• chr5-150676831-G-A
• NM_001122853.3:c.712G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001122853.3(MYOZ3):​c.712G>A​(p.Ala238Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOZ3 NM_001122853.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.83
• Publications: 0 publications found

Genes affected

MYOZ3 (HGNC:18565): (myozenin 3) The protein encoded by this gene is specifically expressed in the skeletal muscle, and belongs to the myozenin family. Members of this family function as calcineurin-interacting proteins that help tether calcineurin to the sarcomere of cardiac and skeletal muscle. They play an important role in modulation of calcineurin signaling. [provided by RefSeq, Apr 2012]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122853.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ3	NM_001122853.3	MANE Select	c.712G>A	p.Ala238Thr	missense	Exon 7 of 7	NP_001116325.1	Q8TDC0-1
	MYOZ3	NM_133371.5		c.712G>A	p.Ala238Thr	missense	Exon 7 of 7	NP_588612.2	Q8TDC0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ3	ENST00000517768.6	TSL:1 MANE Select	c.712G>A	p.Ala238Thr	missense	Exon 7 of 7	ENSP00000428815.1	Q8TDC0-1
	MYOZ3	ENST00000297130.4	TSL:1	c.712G>A	p.Ala238Thr	missense	Exon 7 of 7	ENSP00000297130.4	Q8TDC0-1
	MYOZ3	ENST00000456566.2	TSL:1	n.758G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.61	D
MetaSVM	Benign	-0.81	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		1.8
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.42
Sift	Benign	0.085	T
Sift4G	Benign	0.095	T
Polyphen		1.0	D
Vest4		0.48
MutPred		0.65		Gain of phosphorylation at A238 (P = 0.043)
MVP		0.84
MPC		0.90
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.098
gMVP		0.36
Mutation Taster		=79/21	polymorphism

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

hg19: chr5-150056393;