NM_004130.4:c.481+176_481+179dupGTGT

Variant names:

• chr3-148997054-T-TTGTG
• rs10571382
• NM_004130.4:c.481+176_481+179dupGTGT

Variant summary

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

The NM_004130.4(GYG1):​c.481+176_481+179dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00241 in 606,590 control chromosomes in the GnomAD database, including 6 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (6 hom.)
• Consequence: GYG1 NM_004130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.285
• 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 eas. GnomAd4 allele frequency = 0.00209 (313/149818) while in subpopulation EAS AF = 0.00234 (12/5118). AF 95% confidence interval is 0.00196. There are 0 homozygotes in GnomAd4. There are 140 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 6 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	NM_004130.4	MANE Select	c.481+176_481+179dupGTGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+176_481+179dupGTGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+176_481+179dupGTGT		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+150_481+151insTGTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+150_481+151insTGTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+150_481+151insTGTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.00209 AC: 313 AN: 149702 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00235

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000266

Gnomad ASJ AF: 0.0139

Gnomad EAS AF: 0.00234

Gnomad SAS AF: 0.00233

Gnomad FIN AF: 0.000884

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00245

GnomAD4 exome AF: 0.00252 AC: 1150 AN: 456772 Hom.: 6 AF XY: 0.00264 AC XY: 643 AN XY: 243786

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00695 AC: 89 AN: 12810

American (AMR) AF: 0.000789 AC: 19 AN: 24078

Ashkenazi Jewish (ASJ) AF: 0.0116 AC: 171 AN: 14700

East Asian (EAS) AF: 0.000865 AC: 25 AN: 28888

South Asian (SAS) AF: 0.00314 AC: 157 AN: 49998

European-Finnish (FIN) AF: 0.000971 AC: 28 AN: 28848

Middle Eastern (MID) AF: 0.00238 AC: 5 AN: 2104

European-Non Finnish (NFE) AF: 0.00214 AC: 577 AN: 269430

Other (OTH) AF: 0.00305 AC: 79 AN: 25916

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.00209 AC: 313 AN: 149818 Hom.: 0 Cov.: 0 AF XY: 0.00192 AC XY: 140 AN XY: 73098

African (AFR) AF: 0.00234 AC: 95 AN: 40630

American (AMR) AF: 0.000266 AC: 4 AN: 15046

Ashkenazi Jewish (ASJ) AF: 0.0139 AC: 48 AN: 3452

East Asian (EAS) AF: 0.00234 AC: 12 AN: 5118

South Asian (SAS) AF: 0.00233 AC: 11 AN: 4716

European-Finnish (FIN) AF: 0.000884 AC: 9 AN: 10182

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00191 AC: 129 AN: 67416

Other (OTH) AF: 0.00242 AC: 5 AN: 2062

Alfa AF: 0.000876 Hom.: 193

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
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;