rs200322277

Variant names:

• chr5-150670633-C-T
• rs200322277
• NM_001122853.3:c.211C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150670633-C-T
• chr5-150670633-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001122853.3(MYOZ3):​c.211C>T​(p.Arg71Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,606,984 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R71Q) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000023 (0 hom.)
• Consequence: MYOZ3 NM_001122853.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.545
• Publications: 1 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.091885656).

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.211C>T	p.Arg71Trp	missense	Exon 3 of 7	NP_001116325.1	Q8TDC0-1
	MYOZ3	NM_133371.5		c.211C>T	p.Arg71Trp	missense	Exon 3 of 7	NP_588612.2	Q8TDC0-1
	MYOZ3-AS1	NR_186480.1		n.529G>A		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ3	ENST00000517768.6	TSL:1 MANE Select	c.211C>T	p.Arg71Trp	missense	Exon 3 of 7	ENSP00000428815.1	Q8TDC0-1
	MYOZ3	ENST00000297130.4	TSL:1	c.211C>T	p.Arg71Trp	missense	Exon 3 of 7	ENSP00000297130.4	Q8TDC0-1
	MYOZ3	ENST00000873985.1		c.211C>T	p.Arg71Trp	missense	Exon 2 of 6	ENSP00000544044.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152010 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000567 AC: 14 AN: 247036 AF XY: 0.0000523

Gnomad AFR exome AF: 0.0000627

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000492

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.0000234 AC: 34 AN: 1454858 Hom.: 0 Cov.: 31 AF XY: 0.0000235 AC XY: 17 AN XY: 722550

African (AFR) AF: 0.0000300 AC: 1 AN: 33362

American (AMR) AF: 0.0000225 AC: 1 AN: 44404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25950

East Asian (EAS) AF: 0.000430 AC: 17 AN: 39490

South Asian (SAS) AF: 0.0000466 AC: 4 AN: 85774

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53042

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000542 AC: 6 AN: 1107024

Other (OTH) AF: 0.0000832 AC: 5 AN: 60062

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152126 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 74378

African (AFR) AF: 0.0000241 AC: 1 AN: 41476

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000122 Hom.: 1

Bravo AF: 0.0000907

ExAC AF: 0.0000412 AC: 5

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.15
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.092	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.55
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.21
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.018	D
Polyphen		0.96	D
Vest4		0.67
MutPred		0.43		Loss of disorder (P = 8e-04)
MVP		0.71
MPC		0.80
ClinPred		0.17	T
GERP RS		3.0
Varity_R		0.15
gMVP		0.22
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: rs200322277; hg19: chr5-150050195;