3-148997054-TTGTGTGTGTGTGTG-TTGTGTGTGTGTGTGTG

Variant names:

• chr3-148997054-T-TTG
• rs10571382
• NM_004130.4:c.481+178_481+179dupGT

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+178_481+179dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 605,964 control chromosomes in the GnomAD database, including 198 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (144 hom., cov: 0)
  • Exomes 𝑓: 0.039 (54 hom.)
• Consequence: GYG1 NM_004130.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 3-148997054-T-TTG is Benign according to our data. Variant chr3-148997054-T-TTG is described in ClinVar as Benign. ClinVar VariationId is 1236135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0501 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+178_481+179dupGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+178_481+179dupGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+178_481+179dupGT		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+151insTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+150_481+151insTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+150_481+151insTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5776 AN: 149686 Hom.: 144 Cov.: 0

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0503

Gnomad ASJ AF: 0.0328

Gnomad EAS AF: 0.0265

Gnomad SAS AF: 0.0561

Gnomad FIN AF: 0.0244

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.0348

GnomAD4 exome AF: 0.0390 AC: 17780 AN: 456162 Hom.: 54 AF XY: 0.0394 AC XY: 9591 AN XY: 243444

African (AFR) AF: 0.0152 AC: 195 AN: 12852

American (AMR) AF: 0.0239 AC: 574 AN: 24054

Ashkenazi Jewish (ASJ) AF: 0.0279 AC: 409 AN: 14682

East Asian (EAS) AF: 0.0226 AC: 653 AN: 28854

South Asian (SAS) AF: 0.0465 AC: 2323 AN: 49922

European-Finnish (FIN) AF: 0.0264 AC: 761 AN: 28788

Middle Eastern (MID) AF: 0.0157 AC: 33 AN: 2102

European-Non Finnish (NFE) AF: 0.0443 AC: 11929 AN: 269028

Other (OTH) AF: 0.0349 AC: 903 AN: 25880

GnomAD4 genome AF: 0.0386 AC: 5776 AN: 149802 Hom.: 144 Cov.: 0 AF XY: 0.0375 AC XY: 2737 AN XY: 73084

African (AFR) AF: 0.0174 AC: 706 AN: 40624

American (AMR) AF: 0.0501 AC: 754 AN: 15044

Ashkenazi Jewish (ASJ) AF: 0.0328 AC: 113 AN: 3450

East Asian (EAS) AF: 0.0262 AC: 134 AN: 5118

South Asian (SAS) AF: 0.0556 AC: 262 AN: 4716

European-Finnish (FIN) AF: 0.0244 AC: 248 AN: 10180

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0515 AC: 3474 AN: 67412

Other (OTH) AF: 0.0383 AC: 79 AN: 2062

Alfa AF: 0.0398 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		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;