dbSNP rs111848296: GYG1:c.7+96C>G (chr3-148991743-C-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004130.4(GYG1):c.7+96C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00667 in 1,035,472 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 232 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 115 hom. )

Consequence

GYG1
NM_004130.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.843

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

polyglucosan body myopathy type 2
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics
glycogen storage disease XV
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

GYG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 3-148991743-C-G is Benign according to our data. Variant chr3-148991743-C-G is described in ClinVar as Benign. ClinVar VariationId is 675513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0995 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004130.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GYG1	NM_004130.4	MANE Select	c.7+96C>G	intron	N/A	NP_004121.2
GYG1	NM_001184720.2		c.7+96C>G	intron	N/A	NP_001171649.1	P46976-2
GYG1	NM_001184721.2		c.7+96C>G	intron	N/A	NP_001171650.1	P46976-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GYG1	ENST00000345003.9	TSL:1 MANE Select	c.7+96C>G	intron	N/A	ENSP00000340736.4	P46976-1
GYG1	ENST00000296048.10	TSL:1	c.7+96C>G	intron	N/A	ENSP00000296048.6	P46976-2
GYG1	ENST00000484197.5	TSL:1	c.7+96C>G	intron	N/A	ENSP00000420683.1	P46976-3

Frequencies

GnomAD3 genomes

AF:

0.0291

AC:

4424

AN:

152098

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000529

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.00279

AC:

2463

AN:

883264

Hom.:

115

AF XY:

0.00244

AC XY:

1097

AN XY:

450222

show subpopulations

African (AFR)

AF:

0.104

AC:

1872

AN:

18086

American (AMR)

AF:

0.00629

AC:

164

AN:

26072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18968

East Asian (EAS)

AF:

0.00

AC:

AN:

29614

South Asian (SAS)

AF:

0.000256

AC:

AN:

62382

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32248

Middle Eastern (MID)

AF:

0.00406

AC:

AN:

2956

European-Non Finnish (NFE)

AF:

0.000236

AC:

154

AN:

652322

Other (OTH)

AF:

0.00603

AC:

245

AN:

40616

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

237

355

474

592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0292

AC:

4440

AN:

152208

Hom.:

232

Cov.:

AF XY:

0.0282

AC XY:

2097

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.102

AC:

4242

AN:

41544

American (AMR)

AF:

0.00830

AC:

127

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000529

AC:

AN:

67990

Other (OTH)

AF:

0.0161

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

202

404

606

808

1010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0216

Hom.:

Bravo

AF:

0.0320

Asia WGS

AF:

0.00579

AC:

AN:

3468

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.4

(source)

DANN

Benign

0.74

PhyloP100

0.84

PromoterAI

-0.056

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over