5-150672482-C-T

Variant names:

• chr5-150672482-C-T
• rs531676191
• NM_001122853.3:c.567C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001122853.3(MYOZ3):​c.567C>T​(p.Asn189Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: MYOZ3 NM_001122853.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.75
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.359053).
• BP7: Synonymous conserved (PhyloP=-4.75 with no splicing effect.

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.567C>T	p.Asn189Asn	synonymous	Exon 6 of 7	NP_001116325.1	Q8TDC0-1
	MYOZ3	NM_133371.5		c.567C>T	p.Asn189Asn	synonymous	Exon 6 of 7	NP_588612.2	Q8TDC0-1
	MYOZ3-AS1	NR_186480.1		n.-13G>A		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ3	ENST00000517768.6	TSL:1 MANE Select	c.567C>T	p.Asn189Asn	synonymous	Exon 6 of 7	ENSP00000428815.1	Q8TDC0-1
	MYOZ3	ENST00000297130.4	TSL:1	c.567C>T	p.Asn189Asn	synonymous	Exon 6 of 7	ENSP00000297130.4	Q8TDC0-1
	MYOZ3	ENST00000520112.1	TSL:4	c.316C>T	p.Arg106*	stop_gained	Exon 1 of 2	ENSP00000429439.1	E5RII7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000454 AC: 1 AN: 220062 AF XY: 0.00000842

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000990

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1423738 Hom.: 0 Cov.: 36 AF XY: 0.00000142 AC XY: 1 AN XY: 703730

African (AFR) AF: 0.00 AC: 0 AN: 32328

American (AMR) AF: 0.00 AC: 0 AN: 39758

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23780

East Asian (EAS) AF: 0.00 AC: 0 AN: 39120

South Asian (SAS) AF: 0.00 AC: 0 AN: 81766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5576

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090610

Other (OTH) AF: 0.00 AC: 0 AN: 58552

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.21
DANN	Benign	0.94
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.013	N
PhyloP100		-4.8
Vest4		0.068
GERP RS		-9.6
PromoterAI		0.022	Neutral
Mutation Taster		=165/35	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: rs531676191; hg19: chr5-150052044;