9-34370913-C-G

Variant names:

• chr9-34370913-C-G
• rs750307451
• NM_020702.5:c.2031G>C

Variant summary

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

The NM_020702.5(MYORG):​c.2031G>C​(p.Leu677Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L677L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MYORG NM_020702.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.50
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.2031G>C	p.Leu677Phe	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.2031G>C	p.Leu677Phe	missense	Exon 2 of 2	ENSP00000297625.8	Q6NSJ0
	MYORG	ENST00000896633.1		c.2031G>C	p.Leu677Phe	missense	Exon 2 of 2	ENSP00000566692.1
	MYORG	ENST00000896634.1		c.2031G>C	p.Leu677Phe	missense	Exon 2 of 2	ENSP00000566693.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.71	D
MetaSVM	Pathogenic	0.87	D
PhyloP100		1.5
PrimateAI	Uncertain	0.74	T
REVEL	Pathogenic	0.81
Sift4G	Uncertain	0.0080	D
Polyphen		0.96	D
Vest4		0.39
MutPred		0.89		Gain of sheet (P = 0.1208)
MVP		0.37
MPC		0.89
ClinPred		0.70	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.87
Mutation Taster		=10/90	disease causing

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: rs750307451; hg19: chr9-34370911;