Genetic Variant MYOZ3:p.Arg71Arg (chr5-150670635-G-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7

The NM_001122853.3(MYOZ3):c.213G>A(p.Arg71Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000249 in 1,607,680 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: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MYOZ3
NM_001122853.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.558

Publications

0 publications found

Variant links:

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 links:

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

MYOZ3-AS1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_001122853.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=0.558 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOZ3	NM_001122853.3	MANE Select	c.213G>A	p.Arg71Arg	synonymous	Exon 3 of 7	NP_001116325.1	Q8TDC0-1
MYOZ3	NM_133371.5		c.213G>A	p.Arg71Arg	synonymous	Exon 3 of 7	NP_588612.2	Q8TDC0-1
MYOZ3-AS1	NR_186480.1		n.527C>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOZ3	ENST00000517768.6	TSL:1 MANE Select	c.213G>A	p.Arg71Arg	synonymous	Exon 3 of 7	ENSP00000428815.1	Q8TDC0-1
MYOZ3	ENST00000297130.4	TSL:1	c.213G>A	p.Arg71Arg	synonymous	Exon 3 of 7	ENSP00000297130.4	Q8TDC0-1
MYOZ3	ENST00000873985.1		c.213G>A	p.Arg71Arg	synonymous	Exon 2 of 6	ENSP00000544044.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

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

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1455606

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722972

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33366

American (AMR)

AF:

0.00

AC:

AN:

44486

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39528

South Asian (SAS)

AF:

0.00

AC:

AN:

85874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53036

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1107466

Other (OTH)

AF:

0.00

AC:

AN:

60092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152074

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41368

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.4

(source)

DANN

Benign

0.80

PhyloP100

0.56

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over