Variant 1-24058943-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000374434.4(MYOM3):c.4031C>G(p.Ala1344Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000559 in 1,611,412 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

MYOM3
ENST00000374434.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.23

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM3	NM_152372.4 linkuse as main transcript	c.4031C>G	p.Ala1344Gly	missense_variant	36/37	ENST00000374434.4	NP_689585.3
LOC107984931	XR_001737929.1 linkuse as main transcript	n.275+3029G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOM3	ENST00000374434.4 linkuse as main transcript	c.4031C>G	p.Ala1344Gly	missense_variant	36/37	1	NM_152372.4	ENSP00000363557	P1	Q5VTT5-1
	ENST00000439239.2 linkuse as main transcript	n.178-5104G>C		intron_variant, non_coding_transcript_variant		5
MYOM3	ENST00000338909.9 linkuse as main transcript	c.710C>G	p.Ala237Gly	missense_variant	9/10	2		ENSP00000342689		Q5VTT5-3
MYOM3	ENST00000448831.1 linkuse as main transcript	n.188-2617C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

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:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

245152

Hom.:

AF XY:

0.0000302

AC XY:

AN XY:

132642

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000338

Gnomad SAS 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:

0.00000548

AC:

AN:

1459292

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725568

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 29, 2023

The c.4031C>G (p.A1344G) alteration is located in exon 36 (coding exon 35) of the MYOM3 gene. This alteration results from a C to G substitution at nucleotide position 4031, causing the alanine (A) at amino acid position 1344 to be replaced by a glycine (G). 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

Pathogenic

0.58

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.075

.;T

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.078

MetaRNN

Uncertain

0.60

D;D

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.5

.;L

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

0.90

P;D

Vest4

0.57

MutPred

0.65

.;Gain of catalytic residue at A1344 (P = 0.1083);

MVP

0.52

MPC

0.47

ClinPred

0.89

GERP RS

4.6

Varity_R

0.44

gMVP

0.72

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

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