chr5-150671881-G-T

Variant names:

• chr5-150671881-G-T
• rs1758921122
• NM_001122853.3:c.397G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122853.3(MYOZ3):​c.397G>T​(p.Val133Phe) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V133I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYOZ3 NM_001122853.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• 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]

MYOZ3-AS1 (HGNC:40846): (MYOZ3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20106879).

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.397G>T	p.Val133Phe	missense	Exon 5 of 7	NP_001116325.1	Q8TDC0-1
	MYOZ3	NM_133371.5		c.397G>T	p.Val133Phe	missense	Exon 5 of 7	NP_588612.2	Q8TDC0-1
	MYOZ3-AS1	NR_186480.1		n.354+235C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ3	ENST00000517768.6	TSL:1 MANE Select	c.397G>T	p.Val133Phe	missense	Exon 5 of 7	ENSP00000428815.1	Q8TDC0-1
	MYOZ3	ENST00000297130.4	TSL:1	c.397G>T	p.Val133Phe	missense	Exon 5 of 7	ENSP00000297130.4	Q8TDC0-1
	MYOZ3	ENST00000873985.1		c.397G>T	p.Val133Phe	missense	Exon 4 of 6	ENSP00000544044.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.068	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.54
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.13
Sift	Benign	0.054	T
Sift4G	Uncertain	0.038	D
Polyphen		0.91	P
Vest4		0.14
MutPred		0.49		Gain of glycosylation at P134 (P = 0.1419)
MVP		0.59
MPC		0.79
ClinPred		0.69	D
GERP RS		-1.4
PromoterAI		-0.025	Neutral
Varity_R		0.083
gMVP		0.32
Mutation Taster		=98/2	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

dbSNP: rs1758921122; hg19: chr5-150051443;