chr4-119135955-C-T

Variant names:

• chr4-119135955-C-T
• rs146320826
• NM_016599.5:c.-42C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_016599.5(MYOZ2):​c.-42C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00406 in 160,434 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (0 hom.)
• Consequence: MYOZ2 NM_016599.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.423
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 4-119135955-C-T is Benign according to our data. Variant chr4-119135955-C-T is described in ClinVar as Benign. ClinVar VariationId is 138411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 629 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.-42C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_057683.1	Q9NPC6
	MYOZ2	NM_016599.5	MANE Select	c.-42C>T		5_prime_UTR	Exon 1 of 6	NP_057683.1	Q9NPC6
	MYOZ2	NM_001440645.1		c.-42C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001427574.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOZ2	ENST00000307128.6	TSL:1 MANE Select	c.-42C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000306997.6	Q9NPC6
	MYOZ2	ENST00000307128.6	TSL:1 MANE Select	c.-42C>T		5_prime_UTR	Exon 1 of 6	ENSP00000306997.6	Q9NPC6
	MYOZ2	ENST00000958711.1		c.-42C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000628770.1

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 629 AN: 152154 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.0103

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00570

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00270 AC: 22 AN: 8162 Hom.: 0 Cov.: 0 AF XY: 0.00211 AC XY: 9 AN XY: 4268

African (AFR) AF: 0.00 AC: 0 AN: 46

American (AMR) AF: 0.00579 AC: 8 AN: 1382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 84

East Asian (EAS) AF: 0.00 AC: 0 AN: 302

South Asian (SAS) AF: 0.00142 AC: 1 AN: 704

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 178

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 8

European-Non Finnish (NFE) AF: 0.00255 AC: 13 AN: 5094

Other (OTH) AF: 0.00 AC: 0 AN: 364

GnomAD4 genome AF: 0.00413 AC: 629 AN: 152272 Hom.: 4 Cov.: 32 AF XY: 0.00466 AC XY: 347 AN XY: 74454

African (AFR) AF: 0.00111 AC: 46 AN: 41556

American (AMR) AF: 0.00242 AC: 37 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4828

European-Finnish (FIN) AF: 0.0103 AC: 109 AN: 10598

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00570 AC: 388 AN: 68024

Other (OTH) AF: 0.00378 AC: 8 AN: 2116

Alfa AF: 0.00408 Hom.: 2

Bravo AF: 0.00356

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.9
DANN	Benign	0.92
PhyloP100		0.42
PromoterAI		-0.039	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: rs146320826; hg19: chr4-120057110;