Genetic Variant NM_152372.4:c.3398A>G (chr1-24067046-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152372.4(MYOM3):c.3398A>G(p.Asp1133Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000241 in 1,577,598 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

MYOM3
NM_152372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1131168).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152372.4. 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
	MYOM3	NM_152372.4	MANE Select	c.3398A>G	p.Asp1133Gly	missense	Exon 28 of 37	NP_689585.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOM3	ENST00000374434.4	TSL:1 MANE Select	c.3398A>G	p.Asp1133Gly	missense	Exon 28 of 37	ENSP00000363557.3	Q5VTT5-1
MYOM3	ENST00000958997.1		c.3458A>G	p.Asp1153Gly	missense	Exon 28 of 37	ENSP00000629056.1
MYOM3	ENST00000959000.1		c.3398A>G	p.Asp1133Gly	missense	Exon 27 of 36	ENSP00000629059.1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.000479

GnomAD2 exomes

AF:

0.0000411

AC:

AN:

194644

AF XY:

0.0000381

show subpopulations

Gnomad AFR exome

AF:

0.000635

Gnomad AMR exome

AF:

0.0000334

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000133

AC:

AN:

1425454

Hom.:

Cov.:

AF XY:

0.0000113

AC XY:

AN XY:

705774

show subpopulations

African (AFR)

AF:

0.000521

AC:

AN:

32656

American (AMR)

AF:

0.0000246

AC:

AN:

40730

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25532

East Asian (EAS)

AF:

0.00

AC:

AN:

37984

South Asian (SAS)

AF:

0.00

AC:

AN:

81832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50476

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1091684

Other (OTH)

AF:

0.0000170

AC:

AN:

58834

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000125

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.000362

AC:

AN:

41424

American (AMR)

AF:

0.000196

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.000479

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000331

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000497

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000335

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.050

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.7

PhyloP100

4.2

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.29

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.031

Polyphen

0.90

Vest4

0.35

MVP

0.37

MPC

0.16

ClinPred

0.63

GERP RS

5.3

PromoterAI

-0.013

Neutral

(source)

Varity_R

0.43

gMVP

0.63

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over