NM_020702.5:c.595C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_020702.5(MYORG):c.595C>A(p.Arg199Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 1,598,822 control chromosomes in the GnomAD database, including 1,176 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.029 ( 101 hom., cov: 33)

Exomes 𝑓: 0.035 ( 1075 hom. )

Consequence

MYORG
NM_020702.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.81

Variant links:

Genes affected

MYORG (HGNC:19918): (myogenesis regulating glycosidase (putative)) Predicted to enable hydrolase activity, hydrolyzing O-glycosyl compounds. Involved in skeletal muscle fiber development. Predicted to be located in endoplasmic reticulum membrane and nuclear membrane. Implicated in basal ganglia calcification. [provided by Alliance of Genome Resources, Apr 2022]

MYORG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015852451).

BP6

Variant 9-34372349-G-T is Benign according to our data. Variant chr9-34372349-G-T is described in ClinVar as [Benign]. Clinvar id is 1164440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.029 (4416/152274) while in subpopulation NFE AF= 0.0408 (2771/68000). AF 95% confidence interval is 0.0395. There are 101 homozygotes in gnomad4. There are 2220 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 101 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYORG	NM_020702.5 link	c.595C>A	p.Arg199Ser	missense_variant	Exon 2 of 2	ENST00000297625.8	NP_065753.2	Q6NSJ0
MYORG	XM_011517966.4 link	c.595C>A	p.Arg199Ser	missense_variant	Exon 2 of 2		XP_011516268.1	Q6NSJ0
MYORG	XM_017014930.3 link	c.595C>A	p.Arg199Ser	missense_variant	Exon 2 of 2		XP_016870419.1	Q6NSJ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYORG	ENST00000297625.8 link	c.595C>A	p.Arg199Ser	missense_variant	Exon 2 of 2	1	NM_020702.5	ENSP00000297625.8		Q6NSJ0
MYORG	ENST00000379142.3 link	c.217-18C>A		intron_variant	Intron 1 of 1	5		ENSP00000368437.2		X6RA92

Frequencies

GnomAD3 genomes

AF:

0.0290

AC:

4417

AN:

152156

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00632

Gnomad AMI

AF:

0.0680

Gnomad AMR

AF:

0.0217

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0147

Gnomad FIN

AF:

0.0743

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.0297

AC:

6414

AN:

215868

Hom.:

142

AF XY:

0.0295

AC XY:

3491

AN XY:

118400

show subpopulations

Gnomad AFR exome

AF:

0.00644

Gnomad AMR exome

AF:

0.0122

Gnomad ASJ exome

AF:

0.0252

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.0736

Gnomad NFE exome

AF:

0.0392

Gnomad OTH exome

AF:

0.0287

GnomAD4 exome

AF:

0.0353

AC:

51004

AN:

1446548

Hom.:

1075

Cov.:

AF XY:

0.0347

AC XY:

24961

AN XY:

718556

show subpopulations

Gnomad4 AFR exome

AF:

0.00520

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.0253

Gnomad4 EAS exome

AF:

0.0000516

Gnomad4 SAS exome

AF:

0.0165

Gnomad4 FIN exome

AF:

0.0732

Gnomad4 NFE exome

AF:

0.0385

Gnomad4 OTH exome

AF:

0.0306

GnomAD4 genome

AF:

0.0290

AC:

4416

AN:

152274

Hom.:

101

Cov.:

AF XY:

0.0298

AC XY:

2220

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00628

Gnomad4 AMR

AF:

0.0217

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0147

Gnomad4 FIN

AF:

0.0743

Gnomad4 NFE

AF:

0.0408

Gnomad4 OTH

AF:

0.0246

Alfa

AF:

0.0370

Hom.:

Bravo

AF:

0.0237

ESP6500AA

AF:

0.00627

AC:

ESP6500EA

AF:

0.0351

AC:

293

ExAC

AF:

0.0268

AC:

3223

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 16, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

MYORG-related disorder

Benign:1

Feb 07, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0012

Eigen

Benign

-0.17

Eigen_PC

Benign

0.067

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.81

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.43

REVEL

Benign

0.10

Sift

Benign

0.18

Sift4G

Benign

0.53

Polyphen

0.010

Vest4

0.052

MPC

0.60

ClinPred

0.013

GERP RS

5.7

Varity_R

0.21

gMVP

0.50

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