Genetic Variant MYOM3:p.Asp926Asn (chr1-24075401-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152372.4(MYOM3):c.2776G>A(p.Asp926Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000411 in 1,460,066 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: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MYOM3
NM_152372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.47

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 made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36432058).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM3	NM_152372.4 link	c.2776G>A	p.Asp926Asn	missense_variant	Exon 22 of 37	ENST00000374434.4	NP_689585.3	Q5VTT5-1
MYOM3-AS1	XR_001737930.2 link	n.82-6353C>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYOM3	ENST00000374434.4 link	c.2776G>A	p.Asp926Asn	missense_variant	Exon 22 of 37	1	NM_152372.4	ENSP00000363557.3	Q5VTT5-1
MYOM3-AS1	ENST00000429191.1 link	n.70-6349C>T		intron_variant	Intron 1 of 2	3
ENSG00000225315	ENST00000439239.2 link	n.404+11128C>T		intron_variant	Intron 3 of 3	5
MYOM3	ENST00000448831.1 link	n.187+8545G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460066

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726398

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:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2776G>A (p.D926N) alteration is located in exon 22 (coding exon 21) of the MYOM3 gene. This alteration results from a G to A substitution at nucleotide position 2776, causing the aspartic acid (D) at amino acid position 926 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.046

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.019

MetaRNN

Benign

0.36

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.8

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.24

Sift

Uncertain

0.023

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.32

MutPred

0.28

Gain of sheet (P = 0.0827);

MVP

0.50

MPC

0.43

ClinPred

0.99

GERP RS

6.2

Varity_R

0.26

gMVP

0.43

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over