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

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004130.4(GYG1):​c.481+176_481+179delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 596,190 control chromosomes in the GnomAD database, including 15,635 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.34 (8498 hom., cov: 0)
  • Exomes 𝑓: 0.29 (7137 hom.)
• Consequence: GYG1 NM_004130.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 3-148997054-TTGTG-T is Benign according to our data. Variant chr3-148997054-TTGTG-T is described in ClinVar as Benign. ClinVar VariationId is 1263024.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

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+179delGTGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+176_481+179delGTGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+176_481+179delGTGT		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+154delTGTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+151_481+154delTGTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+151_481+154delTGTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 50767 AN: 149478 Hom.: 8495 Cov.: 0

Gnomad AFR AF: 0.369

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.415

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.289 AC: 128892 AN: 446598 Hom.: 7137 AF XY: 0.283 AC XY: 67519 AN XY: 238448

African (AFR) AF: 0.314 AC: 3939 AN: 12532

American (AMR) AF: 0.274 AC: 6413 AN: 23390

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 4417 AN: 14342

East Asian (EAS) AF: 0.319 AC: 8725 AN: 27382

South Asian (SAS) AF: 0.239 AC: 11727 AN: 48980

European-Finnish (FIN) AF: 0.351 AC: 9999 AN: 28454

Middle Eastern (MID) AF: 0.303 AC: 617 AN: 2034

European-Non Finnish (NFE) AF: 0.286 AC: 75537 AN: 264242

Other (OTH) AF: 0.298 AC: 7518 AN: 25242

GnomAD4 genome AF: 0.340 AC: 50799 AN: 149592 Hom.: 8498 Cov.: 0 AF XY: 0.340 AC XY: 24793 AN XY: 72956

African (AFR) AF: 0.369 AC: 14962 AN: 40574

American (AMR) AF: 0.335 AC: 5027 AN: 15004

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1259 AN: 3450

East Asian (EAS) AF: 0.292 AC: 1497 AN: 5118

South Asian (SAS) AF: 0.281 AC: 1322 AN: 4706

European-Finnish (FIN) AF: 0.415 AC: 4211 AN: 10156

Middle Eastern (MID) AF: 0.318 AC: 93 AN: 292

European-Non Finnish (NFE) AF: 0.319 AC: 21463 AN: 67336

Other (OTH) AF: 0.337 AC: 691 AN: 2052

Alfa AF: 0.242 Hom.: 193

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10571382; hg19: chr3-148714841;