9-34370967-C-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020702.5(MYORG):​c.1977G>C​(p.Thr659Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000731 in 1,613,578 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00074 ( 3 hom. )

Consequence

MYORG
NM_020702.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.382
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
Variant 9-34370967-C-G is Benign according to our data. Variant chr9-34370967-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1681283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.382 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000624 (95/152348) while in subpopulation AMR AF= 0.00196 (30/15304). AF 95% confidence interval is 0.00141. There are 0 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYORGNM_020702.5 linkc.1977G>C p.Thr659Thr synonymous_variant Exon 2 of 2 ENST00000297625.8 NP_065753.2 Q6NSJ0
MYORGXM_011517966.4 linkc.1977G>C p.Thr659Thr synonymous_variant Exon 2 of 2 XP_011516268.1 Q6NSJ0
MYORGXM_017014930.3 linkc.1977G>C p.Thr659Thr synonymous_variant Exon 2 of 2 XP_016870419.1 Q6NSJ0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYORGENST00000297625.8 linkc.1977G>C p.Thr659Thr synonymous_variant Exon 2 of 2 1 NM_020702.5 ENSP00000297625.8 Q6NSJ0

Frequencies

GnomAD3 genomes
AF:
0.000624
AC:
95
AN:
152230
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.000779
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000600
AC:
149
AN:
248502
Hom.:
0
AF XY:
0.000614
AC XY:
83
AN XY:
135078
show subpopulations
Gnomad AFR exome
AF:
0.000195
Gnomad AMR exome
AF:
0.000667
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.0000929
Gnomad NFE exome
AF:
0.000996
Gnomad OTH exome
AF:
0.000993
GnomAD4 exome
AF:
0.000743
AC:
1085
AN:
1461230
Hom.:
3
Cov.:
40
AF XY:
0.000729
AC XY:
530
AN XY:
726918
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000604
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.000170
Gnomad4 NFE exome
AF:
0.000873
Gnomad4 OTH exome
AF:
0.000679
GnomAD4 genome
AF:
0.000624
AC:
95
AN:
152348
Hom.:
0
Cov.:
34
AF XY:
0.000698
AC XY:
52
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.000779
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000873
Hom.:
0
Bravo
AF:
0.000661
EpiCase
AF:
0.000818
EpiControl
AF:
0.00142

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Jan 07, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
CADD
Benign
3.8
DANN
Benign
0.73

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199990841; hg19: chr9-34370965; API