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rs146101365

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_004130.4(GYG1):c.98G>A(p.Arg33Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,613,892 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0020 ( 5 hom. )

Consequence

GYG1
NM_004130.4 missense

Scores

2
17

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 3.09
Variant links:
Genes affected
GYG1 (HGNC:4699): (glycogenin 1) This gene encodes a member of the glycogenin family. Glycogenin is a glycosyltransferase that catalyzes the formation of a short glucose polymer from uridine diphosphate glucose in an autoglucosylation reaction. This reaction is followed by elongation and branching of the polymer, catalyzed by glycogen synthase and branching enzyme, to form glycogen. This gene is expressed in muscle and other tissues. Mutations in this gene result in glycogen storage disease XV. This gene has pseudogenes on chromosomes 1, 8 and 13 respectively. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.013021946).
BP6
Variant 3-148994232-G-A is Benign according to our data. Variant chr3-148994232-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 542121.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GYG1NM_004130.4 linkuse as main transcriptc.98G>A p.Arg33Lys missense_variant 2/8 ENST00000345003.9
GYG1NM_001184720.2 linkuse as main transcriptc.98G>A p.Arg33Lys missense_variant 2/7
GYG1NM_001184721.2 linkuse as main transcriptc.98G>A p.Arg33Lys missense_variant 2/6
GYG1XM_017006275.2 linkuse as main transcriptc.-34-2070G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GYG1ENST00000345003.9 linkuse as main transcriptc.98G>A p.Arg33Lys missense_variant 2/81 NM_004130.4 P46976-1

Frequencies

GnomAD3 genomes
AF:
0.00128
AC:
194
AN:
152068
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000415
Gnomad FIN
AF:
0.000756
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00250
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00153
AC:
385
AN:
251448
Hom.:
1
AF XY:
0.00166
AC XY:
226
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.000405
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000621
Gnomad FIN exome
AF:
0.00134
Gnomad NFE exome
AF:
0.00269
Gnomad OTH exome
AF:
0.00179
GnomAD4 exome
AF:
0.00198
AC:
2887
AN:
1461706
Hom.:
5
Cov.:
32
AF XY:
0.00199
AC XY:
1449
AN XY:
727160
show subpopulations
Gnomad4 AFR exome
AF:
0.000448
Gnomad4 AMR exome
AF:
0.000380
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000742
Gnomad4 FIN exome
AF:
0.00131
Gnomad4 NFE exome
AF:
0.00236
Gnomad4 OTH exome
AF:
0.00137
GnomAD4 genome
AF:
0.00127
AC:
194
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.000968
AC XY:
72
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.000756
Gnomad4 NFE
AF:
0.00250
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00200
Hom.:
0
Bravo
AF:
0.00104
TwinsUK
AF:
0.00189
AC:
7
ALSPAC
AF:
0.00156
AC:
6
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00198
AC:
17
ExAC
AF:
0.00175
AC:
212
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenFeb 01, 2021- -
Likely benign, criteria provided, single submitterclinical testingGeneDxDec 30, 2019- -
Glycogen storage disease XV;C4015452:Polyglucosan body myopathy type 2 Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeJan 22, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.29
Cadd
Benign
23
Dann
Uncertain
0.98
DEOGEN2
Benign
0.29
T;.;.;.;.;T
Eigen
Benign
-0.085
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.69
T;T;T;.;T;T
M_CAP
Benign
0.0072
T
MetaRNN
Benign
0.013
T;T;T;T;T;T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
0.88
L;.;L;.;L;.
MutationTaster
Benign
0.98
D;D;D;D
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-2.1
N;.;N;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.21
T;.;T;T;T;T
Sift4G
Benign
0.21
T;T;T;T;T;T
Polyphen
0.10
B;B;B;B;.;.
Vest4
0.33
MVP
0.78
MPC
0.10
ClinPred
0.019
T
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.45
gMVP
0.55

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: rs146101365; hg19: chr3-148712019; API