chr3-148997054-TTGTGTGTGTGTGTG-T

Variant names:

• chr3-148997054-TTGTGTGTGTGTGTG-T
• rs10571382
• NM_004130.4:c.481+166_481+179delGTGTGTGTGTGTGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000345003.9(GYG1):​c.481+151_481+164delTGTGTGTGTGTGTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00098 in 606,854 control chromosomes in the GnomAD database, including 7 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00085 (2 hom., cov: 0)
  • Exomes 𝑓: 0.0010 (5 hom.)
• Consequence: GYG1 ENST00000345003.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.000848 (127/149816) while in subpopulation AMR AF = 0.00266 (40/15046). AF 95% confidence interval is 0.00201. There are 2 homozygotes in GnomAd4. There are 63 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000345003.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	NM_004130.4	MANE Select	c.481+166_481+179delGTGTGTGTGTGTGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+166_481+179delGTGTGTGTGTGTGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+166_481+179delGTGTGTGTGTGTGT		intron	N/A	NP_001171650.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	ENST00000345003.9	TSL:1 MANE Select	c.481+151_481+164delTGTGTGTGTGTGTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+151_481+164delTGTGTGTGTGTGTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+151_481+164delTGTGTGTGTGTGTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.000855 AC: 128 AN: 149700 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.0000741

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00266

Gnomad ASJ AF: 0.00753

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00169

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.000564

Gnomad OTH AF: 0.00147

GnomAD4 exome AF: 0.00102 AC: 468 AN: 457038 Hom.: 5 AF XY: 0.00106 AC XY: 259 AN XY: 243904

African (AFR) AF: 0.000311 AC: 4 AN: 12862

American (AMR) AF: 0.00270 AC: 65 AN: 24088

Ashkenazi Jewish (ASJ) AF: 0.00781 AC: 115 AN: 14718

East Asian (EAS) AF: 0.00 AC: 0 AN: 28888

South Asian (SAS) AF: 0.00140 AC: 70 AN: 50008

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28848

Middle Eastern (MID) AF: 0.0161 AC: 34 AN: 2106

European-Non Finnish (NFE) AF: 0.000519 AC: 140 AN: 269594

Other (OTH) AF: 0.00154 AC: 40 AN: 25926

GnomAD4 genome AF: 0.000848 AC: 127 AN: 149816 Hom.: 2 Cov.: 0 AF XY: 0.000862 AC XY: 63 AN XY: 73096

African (AFR) AF: 0.0000738 AC: 3 AN: 40630

American (AMR) AF: 0.00266 AC: 40 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.00753 AC: 26 AN: 3452

East Asian (EAS) AF: 0.00 AC: 0 AN: 5118

South Asian (SAS) AF: 0.00148 AC: 7 AN: 4716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10182

Middle Eastern (MID) AF: 0.0342 AC: 10 AN: 292

European-Non Finnish (NFE) AF: 0.000564 AC: 38 AN: 67414

Other (OTH) AF: 0.00145 AC: 3 AN: 2062

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
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10571382; hg19: chr3-148714841;