dbSNP rs148619511: GYG1:p.Thr53Thr (chr3-148996317-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004130.4(GYG1):c.159A>G(p.Thr53Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,610,978 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 11 hom., cov: 32)

Exomes 𝑓: 0.012 ( 147 hom. )

Consequence

GYG1
NM_004130.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.533

Publications

4 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 3-148996317-A-G is Benign according to our data. Variant chr3-148996317-A-G is described in ClinVar as Benign. ClinVar VariationId is 380453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.533 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00763 (1162/152364) while in subpopulation NFE AF = 0.0129 (879/68034). AF 95% confidence interval is 0.0122. There are 11 homozygotes in GnomAd4. There are 515 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

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	HGVSp	Effect	Exon Rank	Protein	UniProt
GYG1	NM_004130.4	MANE Select	c.159A>G	p.Thr53Thr	synonymous	Exon 3 of 8	NP_004121.2
GYG1	NM_001184720.2		c.159A>G	p.Thr53Thr	synonymous	Exon 3 of 7	NP_001171649.1	P46976-2
GYG1	NM_001184721.2		c.159A>G	p.Thr53Thr	synonymous	Exon 3 of 6	NP_001171650.1	P46976-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GYG1	ENST00000345003.9	TSL:1 MANE Select	c.159A>G	p.Thr53Thr	synonymous	Exon 3 of 8	ENSP00000340736.4	P46976-1
GYG1	ENST00000296048.10	TSL:1	c.159A>G	p.Thr53Thr	synonymous	Exon 3 of 7	ENSP00000296048.6	P46976-2
GYG1	ENST00000484197.5	TSL:1	c.159A>G	p.Thr53Thr	synonymous	Exon 3 of 6	ENSP00000420683.1	P46976-3

Frequencies

GnomAD3 genomes

AF:

0.00763

AC:

1162

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00778

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0129

Gnomad OTH

AF:

0.00813

GnomAD2 exomes

AF:

0.00723

AC:

1817

AN:

251224

AF XY:

0.00683

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00308

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00434

Gnomad NFE exome

AF:

0.0124

Gnomad OTH exome

AF:

0.00766

GnomAD4 exome

AF:

0.0121

AC:

17690

AN:

1458614

Hom.:

147

Cov.:

AF XY:

0.0118

AC XY:

8562

AN XY:

725684

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

33382

American (AMR)

AF:

0.00559

AC:

250

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00295

AC:

AN:

26128

East Asian (EAS)

AF:

0.000101

AC:

AN:

39696

South Asian (SAS)

AF:

0.0000929

AC:

AN:

86142

European-Finnish (FIN)

AF:

0.00470

AC:

251

AN:

53420

Middle Eastern (MID)

AF:

0.000238

AC:

AN:

4204

European-Non Finnish (NFE)

AF:

0.0148

AC:

16417

AN:

1110748

Other (OTH)

AF:

0.0102

AC:

613

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

754

1508

2261

3015

3769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.00763

AC:

1162

AN:

152364

Hom.:

Cov.:

AF XY:

0.00691

AC XY:

515

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.00240

AC:

100

AN:

41586

American (AMR)

AF:

0.00777

AC:

119

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0129

AC:

879

AN:

68034

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

118

176

235

294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00956

Hom.:

Bravo

AF:

0.00787

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0108

EpiControl

AF:

0.0117

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Glycogen storage disease XV;C4015452:Polyglucosan body myopathy type 2 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.3

(source)

DANN

Benign

0.70

PhyloP100

-0.53

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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