Genetic Variant MYOM3:p.Val1130Ile (chr1-24067056-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_152372.4(MYOM3):c.3388G>A(p.Val1130Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYOM3
NM_152372.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.68

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07004228).

BP6

Variant 1-24067056-C-T is Benign according to our data. Variant chr1-24067056-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3877211.Status of the report is criteria_provided_single_submitter, 1 stars.

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.3388G>A	p.Val1130Ile	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.3388G>A	p.Val1130Ile	missense	Exon 28 of 37	ENSP00000363557.3	Q5VTT5-1
MYOM3	ENST00000958997.1		c.3448G>A	p.Val1150Ile	missense	Exon 28 of 37	ENSP00000629056.1
MYOM3	ENST00000959000.1		c.3388G>A	p.Val1130Ile	missense	Exon 27 of 36	ENSP00000629059.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1427110

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706696

African (AFR)

AF:

0.00

AC:

AN:

32712

American (AMR)

AF:

0.00

AC:

AN:

40952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25538

East Asian (EAS)

AF:

0.00

AC:

AN:

38138

South Asian (SAS)

AF:

0.00

AC:

AN:

81970

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1092516

Other (OTH)

AF:

0.00

AC:

AN:

58936

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.17

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.041

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.65

M_CAP

Benign

0.019

MetaRNN

Benign

0.070

MetaSVM

Benign

-0.73

MutationAssessor

Benign

1.6

PhyloP100

1.7

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.75

REVEL

Benign

0.041

Sift

Benign

0.067

Sift4G

Benign

0.068

Polyphen

0.0030

Vest4

0.10

MutPred

0.28

Gain of catalytic residue at V1130 (P = 0.039)

MVP

0.12

MPC

0.075

ClinPred

0.21

GERP RS

1.4

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.36

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over