Genetic Variant NM_004130.4:c.481+170_481+179delGTGTGTGTGT (chr3-148997054-TTGTGTGTGTG-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004130.4(GYG1):c.481+170_481+179delGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 606,856 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

GYG1
NM_004130.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.76

Publications

1 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, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, PanelApp Australia, ClinGen
glycogen storage disease XV
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

GYG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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
GYG1	NM_004130.4	MANE Select	c.481+170_481+179delGTGTGTGTGT	intron	N/A	NP_004121.2
GYG1	NM_001184720.2		c.481+170_481+179delGTGTGTGTGT	intron	N/A	NP_001171649.1
GYG1	NM_001184721.2		c.481+170_481+179delGTGTGTGTGT	intron	N/A	NP_001171650.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
GYG1	ENST00000345003.9	TSL:1 MANE Select	c.481+151_481+160delTGTGTGTGTG	intron	N/A	ENSP00000340736.4
GYG1	ENST00000296048.10	TSL:1	c.481+151_481+160delTGTGTGTGTG	intron	N/A	ENSP00000296048.6
GYG1	ENST00000484197.5	TSL:1	c.481+151_481+160delTGTGTGTGTG	intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

149704

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000306

AC:

AN:

457036

Hom.:

AF XY:

0.0000328

AC XY:

AN XY:

243900

show subpopulations

African (AFR)

AF:

0.000155

AC:

AN:

12862

American (AMR)

AF:

0.0000415

AC:

AN:

24088

Ashkenazi Jewish (ASJ)

AF:

0.0000679

AC:

AN:

14718

East Asian (EAS)

AF:

0.00

AC:

AN:

28888

South Asian (SAS)

AF:

0.0000800

AC:

AN:

50010

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2106

European-Non Finnish (NFE)

AF:

0.0000223

AC:

AN:

269590

Other (OTH)

AF:

0.00

AC:

AN:

25926

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000267

AC:

AN:

149820

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73098

show subpopulations

African (AFR)

AF:

0.0000246

AC:

AN:

40632

American (AMR)

AF:

0.00

AC:

AN:

15046

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3452

East Asian (EAS)

AF:

0.000195

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4716

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67416

Other (OTH)

AF:

0.00

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over