1-24074228-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_152372.4(MYOM3):​c.2900G>A​(p.Gly967Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000031 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G967A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MYOM3
NM_152372.4 missense

Scores

12
4
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.11
Variant links:
Genes affected
MYOM3 (HGNC:26679): (myomesin 3) Predicted to enable actin filament binding activity and protein homodimerization activity. Predicted to be involved in muscle contraction. Predicted to be active in M band. [provided by Alliance of Genome Resources, Apr 2022]
MYOM3-AS1 (HGNC:41158): (MYOM3 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.792

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYOM3NM_152372.4 linkc.2900G>A p.Gly967Asp missense_variant Exon 23 of 37 ENST00000374434.4 NP_689585.3 Q5VTT5-1
MYOM3-AS1XR_001737930.2 linkn.81+7386C>T intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYOM3ENST00000374434.4 linkc.2900G>A p.Gly967Asp missense_variant Exon 23 of 37 1 NM_152372.4 ENSP00000363557.3 Q5VTT5-1
MYOM3-AS1ENST00000429191.1 linkn.69+7386C>T intron_variant Intron 1 of 2 3
ENSG00000225315ENST00000439239.2 linkn.404+9955C>T intron_variant Intron 3 of 3 5
MYOM3ENST00000448831.1 linkn.187+9718G>A intron_variant Intron 1 of 1 3

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152084
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461830
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152084
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74276
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000147
Gnomad4 OTH
AF:
0.00
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.96
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
T
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.85
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.81
T
M_CAP
Uncertain
0.094
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Uncertain
0.22
D
MutationAssessor
Pathogenic
3.2
M
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-6.8
D
REVEL
Pathogenic
0.77
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.98
MutPred
0.52
Gain of disorder (P = 0.0588);
MVP
0.55
MPC
0.53
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.89

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: rs1012473029; hg19: chr1-24400718; COSMIC: COSV58389148; API