rs368392953

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2

The NM_016599.5(MYOZ2):ā€‹c.1A>Cā€‹(p.Met1?) variant causes a initiator codon change. The variant allele was found at a frequency of 0.0000031 in 1,613,252 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

MYOZ2
NM_016599.5 initiator_codon

Scores

2
7
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PVS1
Start lost variant, no pathogenic variants between lost start and next in-frame start position. Next in-frame start position is after 18 CDS bases. Genomic position: 119136543. Lost 0.023 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYOZ2NM_016599.5 linkc.1A>C p.Met1? initiator_codon_variant Exon 2 of 6 ENST00000307128.6 NP_057683.1 Q9NPC6
MYOZ2XM_006714234.5 linkc.1A>C p.Met1? initiator_codon_variant Exon 2 of 6 XP_006714297.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYOZ2ENST00000307128.6 linkc.1A>C p.Met1? initiator_codon_variant Exon 2 of 6 1 NM_016599.5 ENSP00000306997.6 Q9NPC6

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250600
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135420
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461024
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726792
show subpopulations
Gnomad4 AFR exome
AF:
0.0000897
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152228
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Pathogenic
0.18
CADD
Benign
22
DANN
Benign
0.96
DEOGEN2
Benign
0.19
T
Eigen
Benign
0.086
Eigen_PC
Uncertain
0.25
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.90
D
M_CAP
Uncertain
0.24
D
MetaRNN
Uncertain
0.64
D
MetaSVM
Benign
-0.46
T
PROVEAN
Benign
-1.2
N
REVEL
Uncertain
0.47
Sift
Pathogenic
0.0
D
Sift4G
Benign
0.12
T
Polyphen
0.028
B
Vest4
0.63
MutPred
0.62
Loss of phosphorylation at S3 (P = 0.1977);
MVP
0.83
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.83
gMVP
0.28

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.

Other links and lift over

dbSNP: rs368392953; hg19: chr4-120057681; API