chr9-34370924-C-T

Variant names:

• chr9-34370924-C-T
• rs1820580189
• NM_020702.5:c.2020G>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_020702.5(MYORG):​c.2020G>A​(p.Asp674Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: MYORG NM_020702.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.81

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.805

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYORG	NM_020702.5	c.2020G>A	p.Asp674Asn	missense_variant	Exon 2 of 2	ENST00000297625.8	NP_065753.2
MYORG	XM_011517966.4	c.2020G>A	p.Asp674Asn	missense_variant	Exon 2 of 2		XP_011516268.1
MYORG	XM_017014930.3	c.2020G>A	p.Asp674Asn	missense_variant	Exon 2 of 2		XP_016870419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYORG	ENST00000297625.8	c.2020G>A	p.Asp674Asn	missense_variant	Exon 2 of 2	1	NM_020702.5	ENSP00000297625.8

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 40

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Sep 21, 2019

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.67
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.81	D
MetaSVM	Uncertain	0.51	D
PrimateAI	Pathogenic	0.80	T
REVEL	Uncertain	0.56
Sift4G	Uncertain	0.047	D
Polyphen		1.0	D
Vest4		0.80
MutPred		0.45		Loss of phosphorylation at Y676 (P = 0.1041);
MVP		0.33
MPC		1.4
ClinPred		0.98	D
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.69
gMVP		0.75

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: rs1820580189; hg19: chr9-34370922;