9-34370823-G-A

Variant names:

• chr9-34370823-G-A
• rs1167824450
• NM_020702.5:c.2121C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_020702.5(MYORG):​c.2121C>T​(p.Ile707Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000348 in 1,434,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I707I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: MYORG NM_020702.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.872
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.872 with no splicing effect.

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.2121C>T	p.Ile707Ile	synonymous	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.2121C>T	p.Ile707Ile	synonymous	Exon 2 of 2	ENSP00000297625.8	Q6NSJ0
	MYORG	ENST00000896633.1		c.2121C>T	p.Ile707Ile	synonymous	Exon 2 of 2	ENSP00000566692.1
	MYORG	ENST00000896634.1		c.2121C>T	p.Ile707Ile	synonymous	Exon 2 of 2	ENSP00000566693.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000834 AC: 2 AN: 239884 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000479

Gnomad NFE exome AF: 0.00000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000348 AC: 5 AN: 1434806 Hom.: 0 Cov.: 40 AF XY: 0.00000282 AC XY: 2 AN XY: 708446

African (AFR) AF: 0.00 AC: 0 AN: 33020

American (AMR) AF: 0.00 AC: 0 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25022

East Asian (EAS) AF: 0.00 AC: 0 AN: 39114

South Asian (SAS) AF: 0.00 AC: 0 AN: 83878

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5670

European-Non Finnish (NFE) AF: 0.00000366 AC: 4 AN: 1092616

Other (OTH) AF: 0.00 AC: 0 AN: 59050

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	5.0
DANN	Benign	0.82
PhyloP100		-0.87

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: rs1167824450; hg19: chr9-34370821; COSMIC: COSV99898781; COSMIC: COSV99898781;