5-150671881-G-A

Variant names:

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

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>A​(p.Val133Ile) 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. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYOZ3 NM_001122853.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.097661644).

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>A	p.Val133Ile	missense	Exon 5 of 7	NP_001116325.1	Q8TDC0-1
	MYOZ3	NM_133371.5		c.397G>A	p.Val133Ile	missense	Exon 5 of 7	NP_588612.2	Q8TDC0-1
	MYOZ3-AS1	NR_186480.1		n.354+235C>T		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>A	p.Val133Ile	missense	Exon 5 of 7	ENSP00000428815.1	Q8TDC0-1
	MYOZ3	ENST00000297130.4	TSL:1	c.397G>A	p.Val133Ile	missense	Exon 5 of 7	ENSP00000297130.4	Q8TDC0-1
	MYOZ3	ENST00000873985.1		c.397G>A	p.Val133Ile	missense	Exon 4 of 6	ENSP00000544044.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1425664 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 707342

African (AFR) AF: 0.00 AC: 0 AN: 32566

American (AMR) AF: 0.00 AC: 0 AN: 39868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25106

East Asian (EAS) AF: 0.00 AC: 0 AN: 37784

South Asian (SAS) AF: 0.00 AC: 0 AN: 83096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098382

Other (OTH) AF: 0.00 AC: 0 AN: 59084

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	Benign	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	11
DANN	Benign	0.96
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.54
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.26	N
REVEL	Benign	0.049
Sift	Benign	0.43	T
Sift4G	Benign	0.45	T
Polyphen		0.56	P
Vest4		0.056
MutPred		0.50		Gain of catalytic residue at S135 (P = 0.189)
MVP		0.37
MPC		0.21
ClinPred		0.15	T
GERP RS		-1.4
PromoterAI		-0.048	Neutral
Varity_R		0.045
gMVP		0.13
Mutation Taster		=88/12	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;