rs146101365

Positions:

chr3-148994232-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

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. 15/21 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

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]

GYG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GYG1	NM_004130.4 linkuse as main transcript	c.98G>A	p.Arg33Lys	missense_variant	2/8	ENST00000345003.9
GYG1	NM_001184720.2 linkuse as main transcript	c.98G>A	p.Arg33Lys	missense_variant	2/7
GYG1	NM_001184721.2 linkuse as main transcript	c.98G>A	p.Arg33Lys	missense_variant	2/6
GYG1	XM_017006275.2 linkuse as main transcript	c.-34-2070G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYG1	ENST00000345003.9 linkuse as main transcript	c.98G>A	p.Arg33Lys	missense_variant	2/8	1	NM_004130.4		P46976-1

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

194

AN:

152068

Hom.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

AF XY:

0.000968

AC XY:

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.:

Bravo

AF:

0.00104

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00175

AC:

212

Asia WGS

AF:

0.000866

AC:

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 submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 30, 2019	- -

Glycogen storage disease XV;C4015452:Polyglucosan body myopathy type 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

T;.;.;.;.;T

Eigen

Benign

-0.085

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.69

T;T;T;.;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.013

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.88

L;.;L;.;L;.

MutationTaster

Benign

0.98

D;D;D;D

PrimateAI

Benign

0.38

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over