dbSNP rs12145360: MYOM3:p.Ile1066Thr (chr1-24068321-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152372.4(MYOM3):c.3197T>C(p.Ile1066Thr) variant causes a missense change. The variant allele was found at a frequency of 0.143 in 1,613,636 control chromosomes in the GnomAD database, including 18,275 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2163 hom., cov: 31)

Exomes 𝑓: 0.14 ( 16112 hom. )

Consequence

MYOM3
NM_152372.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.83

Publications

19 publications found

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 links:

MYOM3-AS1 (HGNC:41158): (MYOM3 antisense RNA 1)

MYOM3-AS1 links:

ENSG00000225315 (HGNC:):

ENSG00000225315 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016693771).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM3	NM_152372.4 link	c.3197T>C	p.Ile1066Thr	missense_variant	Exon 26 of 37	ENST00000374434.4	NP_689585.3
MYOM3-AS1	XR_001737930.2 link	n.81+1479A>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
MYOM3	ENST00000374434.4 link	c.3197T>C	p.Ile1066Thr	missense_variant	Exon 26 of 37	1	NM_152372.4	ENSP00000363557.3
MYOM3-AS1	ENST00000429191.1 link	n.69+1479A>G		intron_variant	Intron 1 of 2	3
ENSG00000225315	ENST00000439239.2 link	n.404+4048A>G		intron_variant	Intron 3 of 3	5
MYOM3	ENST00000448831.1 link	n.188-11995T>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.162

AC:

24629

AN:

151942

Hom.:

2166

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.279

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.292

Gnomad EAS

AF:

0.204

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.163

AC:

40797

AN:

249524

AF XY:

0.168

show subpopulations

Gnomad AFR exome

AF:

0.198

Gnomad AMR exome

AF:

0.135

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.199

Gnomad FIN exome

AF:

0.115

Gnomad NFE exome

AF:

0.136

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.141

AC:

205575

AN:

1461576

Hom.:

16112

Cov.:

AF XY:

0.144

AC XY:

105004

AN XY:

727114

show subpopulations

African (AFR)

AF:

0.196

AC:

6553

AN:

33474

American (AMR)

AF:

0.139

AC:

6202

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

7749

AN:

26130

East Asian (EAS)

AF:

0.178

AC:

7076

AN:

39692

South Asian (SAS)

AF:

0.246

AC:

21214

AN:

86238

European-Finnish (FIN)

AF:

0.114

AC:

6071

AN:

53420

Middle Eastern (MID)

AF:

0.260

AC:

1501

AN:

5768

European-Non Finnish (NFE)

AF:

0.125

AC:

139186

AN:

1111756

Other (OTH)

AF:

0.166

AC:

10023

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

9195

18389

27584

36778

45973

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5200

10400

15600

20800

26000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.162

AC:

24646

AN:

152060

Hom.:

2163

Cov.:

AF XY:

0.165

AC XY:

12248

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.198

AC:

8219

AN:

41476

American (AMR)

AF:

0.161

AC:

2455

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

1012

AN:

3468

East Asian (EAS)

AF:

0.205

AC:

1057

AN:

5164

South Asian (SAS)

AF:

0.247

AC:

1185

AN:

4790

European-Finnish (FIN)

AF:

0.118

AC:

1252

AN:

10596

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8771

AN:

67966

Other (OTH)

AF:

0.177

AC:

375

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1068

2136

3203

4271

5339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.154

Hom.:

5131

Bravo

AF:

0.166

TwinsUK

AF:

0.125

AC:

463

ESP6500AA

AF:

0.178

AC:

715

ESP6500EA

AF:

0.134

AC:

1118

ExAC

AF:

0.164

AC:

19763

Asia WGS

AF:

0.233

AC:

810

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.050

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.010

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.77

PhyloP100

4.8

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.2

Sift

Benign

0.28

Sift4G

Benign

0.10

Vest4

0.059

ClinPred

0.012

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.078

gMVP

0.61

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over