9-34370861-C-G

Variant names:

• chr9-34370861-C-G
• rs773635749
• NM_020702.5:c.2083G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020702.5(MYORG):​c.2083G>C​(p.Val695Leu) 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. 11/17 in silico tools predict a benign 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: 1.22

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.071312726).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYORG	NM_020702.5	c.2083G>C	p.Val695Leu	missense_variant	Exon 2 of 2	ENST00000297625.8	NP_065753.2
MYORG	XM_011517966.4	c.2083G>C	p.Val695Leu	missense_variant	Exon 2 of 2		XP_011516268.1
MYORG	XM_017014930.3	c.2083G>C	p.Val695Leu	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.2083G>C	p.Val695Leu	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

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Dec 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Benign	0.93
DEOGEN2	Benign	0.00064	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.078
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.40	T
PrimateAI	Uncertain	0.54	T
REVEL	Uncertain	0.30
Sift4G	Benign	0.59	T
Polyphen		0.0020	B
Vest4		0.071
MutPred		0.37		Gain of catalytic residue at V695 (P = 0.0455);
MVP		0.16
MPC		0.52
ClinPred		0.29	T
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.12
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs773635749; hg19: chr9-34370859;