rs12377

Positions:

• chr9-34372349-G-A
• chr9-34372349-G-C
• chr9-34372349-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_020702.5(MYORG):​c.595C>T​(p.Arg199Cys) 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. 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 Likely benign.

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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31747264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYORG	NM_020702.5	c.595C>T	p.Arg199Cys	missense_variant	2/2	ENST00000297625.8	NP_065753.2
MYORG	XM_011517966.4	c.595C>T	p.Arg199Cys	missense_variant	2/2		XP_011516268.1
MYORG	XM_017014930.3	c.595C>T	p.Arg199Cys	missense_variant	2/2		XP_016870419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYORG	ENST00000297625.8	c.595C>T	p.Arg199Cys	missense_variant	2/2	1	NM_020702.5	ENSP00000297625.8
MYORG	ENST00000379142.3	c.217-18C>T		intron_variant		5		ENSP00000368437.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 71

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	0.00037	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.023	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.55	T
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.3	D
REVEL	Benign	0.19
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.036	D
Polyphen		0.99	D
Vest4		0.37
MutPred		0.48		Loss of disorder (P = 0.0217);
MVP		0.64
MPC		1.3
ClinPred		0.91	D
GERP RS		5.7
Varity_R		0.12
gMVP		0.64

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

Other links and lift over

dbSNP: rs12377; hg19: chr9-34372347;