rs117556704

Positions:

chr4-119158135-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_016599.5(MYOZ2):c.360A>G(p.Pro120Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,614,116 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0012 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0011 ( 28 hom. )

Consequence

MYOZ2
NM_016599.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.196

Variant links:

Genes affected

MYOZ2 (HGNC:1330): (myozenin 2) The protein encoded by this gene belongs to a family of sarcomeric proteins that bind to calcineurin, a phosphatase involved in calcium-dependent signal transduction in diverse cell types. These family members tether calcineurin to alpha-actinin at the z-line of the sarcomere of cardiac and skeletal muscle cells, and thus they are important for calcineurin signaling. Mutations in this gene cause cardiomyopathy familial hypertrophic type 16, a hereditary heart disorder. [provided by RefSeq, Aug 2011]

MYOZ2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 4-119158135-A-G is Benign according to our data. Variant chr4-119158135-A-G is described in ClinVar as [Benign]. Clinvar id is 45782.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-119158135-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.196 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00125 (190/152302) while in subpopulation EAS AF= 0.0341 (177/5192). AF 95% confidence interval is 0.03. There are 6 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOZ2	NM_016599.5 linkuse as main transcript	c.360A>G	p.Pro120Pro	synonymous_variant	4/6	ENST00000307128.6	NP_057683.1	Q9NPC6
MYOZ2	XM_006714234.5 linkuse as main transcript	c.360A>G	p.Pro120Pro	synonymous_variant	4/6		XP_006714297.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOZ2	ENST00000307128.6 linkuse as main transcript	c.360A>G	p.Pro120Pro	synonymous_variant	4/6	1	NM_016599.5	ENSP00000306997.6		Q9NPC6

Frequencies

GnomAD3 genomes

AF:

0.00125

AC:

190

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00265

AC:

667

AN:

251342

Hom.:

AF XY:

0.00266

AC XY:

361

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0330

Gnomad SAS exome

AF:

0.00137

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00105

AC:

1539

AN:

1461814

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

791

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0331

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000180

Gnomad4 OTH exome

AF:

0.00104

GnomAD4 genome

AF:

0.00125

AC:

190

AN:

152302

Hom.:

Cov.:

AF XY:

0.00154

AC XY:

115

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0341

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000197

Hom.:

Bravo

AF:

0.00171

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 18, 2014	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Nov 20, 2012	Pro120Pro in exon 4 of MYOZ2: This variant is not expected to have clinical sign ificance because it has been identified in 4.2% (24/572) of Asian chromosomes fr om a broad population by the 1000 Genomes project (dbSNP rs117556704). -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Nov 04, 2015

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypertrophic cardiomyopathy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 18, 2024

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 04, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

8.8

DANN

Benign

0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over