chr3-148997054-TTGTGTG-T

Variant names:

• chr3-148997054-TTGTGTG-T
• rs10571382
• NM_004130.4:c.481+174_481+179delGTGTGT

Variant summary

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

The NM_004130.4(GYG1):​c.481+174_481+179delGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 589,580 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 0.00026 (0 hom., cov: 0)
  • Exomes 𝑓: 0.015 (0 hom.)
• Consequence: GYG1 NM_004130.4 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Variant has high frequency in the AFR (0.0183) population. However there is too low homozygotes in high coverage region: (expected more than 18, got 0).

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+174_481+179delGTGTGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+174_481+179delGTGTGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+174_481+179delGTGTGT		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+156delTGTGTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+151_481+156delTGTGTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+151_481+156delTGTGTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.000261 AC: 39 AN: 149564 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000296

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000866

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000197

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000163

Gnomad OTH AF: 0.000491

GnomAD4 exome AF: 0.0150 AC: 6579 AN: 439900 Hom.: 0 AF XY: 0.0146 AC XY: 3422 AN XY: 234962

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

African (AFR) AF: 0.0204 AC: 250 AN: 12272

American (AMR) AF: 0.0165 AC: 383 AN: 23276

Ashkenazi Jewish (ASJ) AF: 0.0165 AC: 233 AN: 14116

East Asian (EAS) AF: 0.0149 AC: 416 AN: 27976

South Asian (SAS) AF: 0.0110 AC: 530 AN: 48332

European-Finnish (FIN) AF: 0.0232 AC: 634 AN: 27330

Middle Eastern (MID) AF: 0.0179 AC: 36 AN: 2016

European-Non Finnish (NFE) AF: 0.0143 AC: 3718 AN: 259692

Other (OTH) AF: 0.0152 AC: 379 AN: 24890

⚠️ 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: 0.000261 AC: 39 AN: 149680 Hom.: 0 Cov.: 0 AF XY: 0.000219 AC XY: 16 AN XY: 73040

African (AFR) AF: 0.000295 AC: 12 AN: 40624

American (AMR) AF: 0.000865 AC: 13 AN: 15034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3446

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4716

European-Finnish (FIN) AF: 0.000197 AC: 2 AN: 10130

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

European-Non Finnish (NFE) AF: 0.000163 AC: 11 AN: 67358

Other (OTH) AF: 0.000486 AC: 1 AN: 2058

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		=99/1	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;