Variant chr1-24075468-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_152372.4(MYOM3):c.2709T>G(p.His903Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYOM3
NM_152372.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.489

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022816926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOM3	NM_152372.4 linkuse as main transcript	c.2709T>G	p.His903Gln	missense_variant	22/37	ENST00000374434.4	NP_689585.3
MYOM3-AS1	XR_001737930.2 linkuse as main transcript	n.82-6286A>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.2709T>G	p.His903Gln	missense_variant	22/37	1	NM_152372.4	ENSP00000363557	P1	Q5VTT5-1
MYOM3-AS1	ENST00000429191.1 linkuse as main transcript	n.70-6282A>C		intron_variant, non_coding_transcript_variant		3
	ENST00000439239.2 linkuse as main transcript	n.404+11195A>C		intron_variant, non_coding_transcript_variant		5
MYOM3	ENST00000448831.1 linkuse as main transcript	n.187+8478T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151868

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00221

AC:

3072

AN:

1392488

Hom.:

Cov.:

AF XY:

0.00205

AC XY:

1417

AN XY:

690794

show subpopulations

Gnomad4 AFR exome

AF:

0.00196

Gnomad4 AMR exome

AF:

0.000356

Gnomad4 ASJ exome

AF:

0.00143

Gnomad4 EAS exome

AF:

0.00109

Gnomad4 SAS exome

AF:

0.000866

Gnomad4 FIN exome

AF:

0.00101

Gnomad4 NFE exome

AF:

0.00253

Gnomad4 OTH exome

AF:

0.00155

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000197

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000209

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Dec 02, 2022

The c.2709T>G (p.H903Q) alteration is located in exon 22 (coding exon 21) of the MYOM3 gene. This alteration results from a T to G substitution at nucleotide position 2709, causing the histidine (H) at amino acid position 903 to be replaced by a glutamine (Q). 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

0.24

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.16

DANN

Benign

0.76

DEOGEN2

Benign

0.0030

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.54

M_CAP

Benign

0.0049

MetaRNN

Benign

0.023

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.5

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.20

PROVEAN

Benign

1.0

REVEL

Benign

0.034

Sift

Benign

0.13

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.11

MutPred

0.43

Loss of sheet (P = 0.0817);

MVP

0.030

MPC

0.086

ClinPred

0.050

GERP RS

-2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.056

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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