4-119135955-C-T

Variant summary

Our verdict is Benign. Variant got -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 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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.423

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 138411.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 629 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOZ2	NM_016599.5	c.-42C>T		5_prime_UTR_variant	1/6	ENST00000307128.6
MYOZ2	XM_006714234.5	c.-42C>T		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOZ2	ENST00000307128.6	c.-42C>T		5_prime_UTR_variant	1/6	1	NM_016599.5	P1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00579

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00142

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00255

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0103

Gnomad4 NFE AF: 0.00570

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00516 Hom.: 2

Bravo AF: 0.00356

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 30, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	8.9
Dann	Benign	0.92

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

Other links and lift over

dbSNP: rs146320826; hg19: chr4-120057110;