Variant chr1-24068224-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_152372.4(MYOM3):c.3294C>T(p.Asp1098=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00419 in 1,608,556 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 65 hom. )

Consequence

MYOM3
NM_152372.4 splice_region, synonymous

Scores

Splicing: ADA: 0.001218

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0910

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 1-24068224-G-A is Benign according to our data. Variant chr1-24068224-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638489.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.091 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM3	NM_152372.4 linkuse as main transcript	c.3294C>T	p.Asp1098=	splice_region_variant, synonymous_variant	26/37	ENST00000374434.4	NP_689585.3
MYOM3-AS1	XR_001737930.2 linkuse as main transcript	n.81+1382G>A		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.3294C>T	p.Asp1098=	splice_region_variant, synonymous_variant	26/37	1	NM_152372.4	ENSP00000363557	P1	Q5VTT5-1
MYOM3-AS1	ENST00000429191.1 linkuse as main transcript	n.69+1382G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000439239.2 linkuse as main transcript	n.404+3951G>A		intron_variant, non_coding_transcript_variant		5
MYOM3	ENST00000448831.1 linkuse as main transcript	n.188-11898C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00571

AC:

851

AN:

149114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000234

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.000790

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0457

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00476

Gnomad OTH

AF:

0.00291

GnomAD3 exomes

AF:

0.00573

AC:

1425

AN:

248852

Hom.:

AF XY:

0.00551

AC XY:

744

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.000199

Gnomad AMR exome

AF:

0.000901

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0393

Gnomad NFE exome

AF:

0.00415

Gnomad OTH exome

AF:

0.00695

GnomAD4 exome

AF:

0.00404

AC:

5894

AN:

1459336

Hom.:

Cov.:

AF XY:

0.00399

AC XY:

2896

AN XY:

726162

show subpopulations

Gnomad4 AFR exome

AF:

0.000253

Gnomad4 AMR exome

AF:

0.000830

Gnomad4 ASJ exome

AF:

0.00348

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.00310

Gnomad4 OTH exome

AF:

0.00404

GnomAD4 genome

AF:

0.00570

AC:

851

AN:

149220

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

529

AN XY:

72988

show subpopulations

Gnomad4 AFR

AF:

0.000233

Gnomad4 AMR

AF:

0.000789

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0457

Gnomad4 NFE

AF:

0.00476

Gnomad4 OTH

AF:

0.00288

Alfa

AF:

0.00357

Hom.:

Bravo

AF:

0.00193

EpiCase

AF:

0.00322

EpiControl

AF:

0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

MYOM3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0012

dbscSNV1_RF

Benign

0.040

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