rs12377

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

basal ganglia calcification, idiopathic, 7, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
bilateral striopallidodentate calcinosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYORG links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_020702.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 101 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020702.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYORG	NM_020702.5	MANE Select	c.595C>A	p.Arg199Ser	missense	Exon 2 of 2	NP_065753.2	Q6NSJ0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYORG	ENST00000297625.8	TSL:1 MANE Select	c.595C>A	p.Arg199Ser	missense	Exon 2 of 2	ENSP00000297625.8	Q6NSJ0
MYORG	ENST00000896633.1		c.595C>A	p.Arg199Ser	missense	Exon 2 of 2	ENSP00000566692.1
MYORG	ENST00000896634.1		c.595C>A	p.Arg199Ser	missense	Exon 2 of 2	ENSP00000566693.1

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

GnomAD2 exomes

AF:

0.0297

AC:

6414

AN:

215868

AF XY:

0.0295

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 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

African (AFR)

AF:

0.00520

AC:

172

AN:

33102

American (AMR)

AF:

0.0137

AC:

584

AN:

42624

Ashkenazi Jewish (ASJ)

AF:

0.0253

AC:

652

AN:

25742

East Asian (EAS)

AF:

0.0000516

AC:

AN:

38730

South Asian (SAS)

AF:

0.0165

AC:

1386

AN:

84172

European-Finnish (FIN)

AF:

0.0732

AC:

3722

AN:

50828

Middle Eastern (MID)

AF:

0.00803

AC:

AN:

5602

European-Non Finnish (NFE)

AF:

0.0385

AC:

42610

AN:

1106004

Other (OTH)

AF:

0.0306

AC:

1831

AN:

59744

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

3254

6508

9763

13017

16271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1496

2992

4488

5984

7480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0290

AC:

4416

AN:

152274

Hom.:

101

Cov.:

AF XY:

0.0298

AC XY:

2220

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.00628

AC:

261

AN:

41570

American (AMR)

AF:

0.0217

AC:

332

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5168

South Asian (SAS)

AF:

0.0147

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0743

AC:

789

AN:

10614

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0408

AC:

2771

AN:

68000

Other (OTH)

AF:

0.0246

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

228

457

685

914

1142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0348

Hom.:

177

Bravo

AF:

0.0237

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

MYORG-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

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

PhyloP100

2.8

PrimateAI

Benign

0.46

PROVEAN

Benign

-0.43

REVEL

Benign

0.10

Sift

Benign

0.18

Sift4G

Benign

0.53

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.21

gMVP

0.50

Mutation Taster

=90/10

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over