rs765512216

Variant names:

• chr9-34370903-T-A
• rs765512216
• NM_020702.5:c.2041A>T

Your query was ambiguous. Multiple possible variants found:

• chr9-34370903-T-A
• chr9-34370903-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate PM2

The NM_020702.5(MYORG):​c.2041A>T​(p.Lys681*) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000274 in 1,461,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: MYORG NM_020702.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21

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 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0485 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYORG	NM_020702.5	c.2041A>T	p.Lys681*	stop_gained	Exon 2 of 2	ENST00000297625.8	NP_065753.2
MYORG	XM_011517966.4	c.2041A>T	p.Lys681*	stop_gained	Exon 2 of 2		XP_011516268.1
MYORG	XM_017014930.3	c.2041A>T	p.Lys681*	stop_gained	Exon 2 of 2		XP_016870419.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYORG	ENST00000297625.8	c.2041A>T	p.Lys681*	stop_gained	Exon 2 of 2	1	NM_020702.5	ENSP00000297625.8

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248778 Hom.: 0 AF XY: 0.00000740 AC XY: 1 AN XY: 135138

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000888

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461020 Hom.: 0 Cov.: 40 AF XY: 0.00000275 AC XY: 2 AN XY: 726694

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ExAC AF: 0.00000827 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.54	D
BayesDel_noAF	Pathogenic	0.54
CADD	Pathogenic	39
DANN	Uncertain	0.99
Eigen	Pathogenic	0.86
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.90	D
Vest4		0.25
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs765512216; hg19: chr9-34370901;