9-34372349-G-C

Variant names:

• chr9-34372349-G-C
• rs12377
• NM_020702.5:c.595C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020702.5(MYORG):​c.595C>G​(p.Arg199Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R199S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYORG NM_020702.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 6 publications found

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: Genomics England PanelApp, Illumina, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1954386).

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>G	p.Arg199Gly	missense	Exon 2 of 2	NP_065753.2	Q6NSJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYORG	ENST00000297625.8	TSL:1 MANE Select	c.595C>G	p.Arg199Gly	missense	Exon 2 of 2	ENSP00000297625.8	Q6NSJ0
	MYORG	ENST00000896633.1		c.595C>G	p.Arg199Gly	missense	Exon 2 of 2	ENSP00000566692.1
	MYORG	ENST00000896634.1		c.595C>G	p.Arg199Gly	missense	Exon 2 of 2	ENSP00000566693.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0049	T
Eigen	Benign	-0.0066
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.78	T
PhyloP100		2.8
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.030
Sift	Benign	0.050	D
Sift4G	Benign	0.25	T
Polyphen		0.14	B
Vest4		0.32
MutPred		0.42		Loss of catalytic residue at R199 (P = 0.0744)
MVP		0.62
MPC		0.76
ClinPred		0.41	T
GERP RS		5.7
PromoterAI		0.029	Neutral
Varity_R		0.28
gMVP		0.61
Mutation Taster		=87/13	polymorphism

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

Other links and lift over

dbSNP: rs12377; hg19: chr9-34372347;