chr4-119135910-A-G

Variant names:

• chr4-119135910-A-G
• rs11559058
• NM_016599.5:c.-87A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_016599.5(MYOZ2):​c.-87A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00949 in 160,594 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0095 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0093 (2 hom.)
• Consequence: MYOZ2 NM_016599.5 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 0.270
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy 16

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 4-119135910-A-G is Benign according to our data. Variant chr4-119135910-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 31785.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0095 (1447/152310) while in subpopulation SAS AF = 0.0313 (151/4826). AF 95% confidence interval is 0.0272. There are 10 homozygotes in GnomAd4. There are 725 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1447 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016599.5. 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
	MYOZ2	NM_016599.5	MANE Select	c.-87A>G		5_prime_UTR	Exon 1 of 6	NP_057683.1	Q9NPC6
	MYOZ2	NM_001440645.1		c.-87A>G		5_prime_UTR	Exon 1 of 7	NP_001427574.1
	MYOZ2	NM_001440646.1		c.-87A>G		5_prime_UTR	Exon 1 of 6	NP_001427575.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ2	ENST00000307128.6	TSL:1 MANE Select	c.-87A>G		5_prime_UTR	Exon 1 of 6	ENSP00000306997.6	Q9NPC6
	MYOZ2	ENST00000958711.1		c.-87A>G		5_prime_UTR	Exon 1 of 7	ENSP00000628770.1
	MYOZ2	ENST00000890356.1		c.-91A>G		5_prime_UTR	Exon 1 of 6	ENSP00000560415.1

Frequencies

GnomAD3 genomes AF: 0.00951 AC: 1447 AN: 152192 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.00674

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0311

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00909

GnomAD4 exome AF: 0.00930 AC: 77 AN: 8284 Hom.: 2 Cov.: 0 AF XY: 0.0105 AC XY: 46 AN XY: 4392

African (AFR) AF: 0.00 AC: 0 AN: 42

American (AMR) AF: 0.00775 AC: 11 AN: 1420

Ashkenazi Jewish (ASJ) AF: 0.0139 AC: 1 AN: 72

East Asian (EAS) AF: 0.00 AC: 0 AN: 296

South Asian (SAS) AF: 0.0256 AC: 17 AN: 664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 148

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 14

European-Non Finnish (NFE) AF: 0.00892 AC: 47 AN: 5272

Other (OTH) AF: 0.00281 AC: 1 AN: 356

GnomAD4 genome AF: 0.00950 AC: 1447 AN: 152310 Hom.: 10 Cov.: 32 AF XY: 0.00974 AC XY: 725 AN XY: 74472

African (AFR) AF: 0.00238 AC: 99 AN: 41578

American (AMR) AF: 0.00673 AC: 103 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5176

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4826

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10622

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0139 AC: 943 AN: 68014

Other (OTH) AF: 0.00900 AC: 19 AN: 2112

Alfa AF: 0.0118 Hom.: 7

Bravo AF: 0.00893

Asia WGS AF: 0.00982 AC: 34 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.9
DANN	Benign	0.76
PhyloP100		0.27
PromoterAI		0.018	Neutral
Mutation Taster		=300/0	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: rs11559058; hg19: chr4-120057065;