chr3-148997054-T-TTGTGTG

Variant names:

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

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+174_481+179dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 606,324 control chromosomes in the GnomAD database, including 191 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (167 hom., cov: 0)
  • Exomes 𝑓: 0.011 (24 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-TTGTGTG is Benign according to our data. Variant chr3-148997054-T-TTGTGTG is described in ClinVar as Benign. ClinVar VariationId is 1265049.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0868 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+174_481+179dupGTGTGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+174_481+179dupGTGTGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+174_481+179dupGTGTGT		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+151insTGTGTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+150_481+151insTGTGTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+150_481+151insTGTGTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.0318 AC: 4760 AN: 149668 Hom.: 168 Cov.: 0

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0188

Gnomad ASJ AF: 0.00579

Gnomad EAS AF: 0.000780

Gnomad SAS AF: 0.00593

Gnomad FIN AF: 0.00246

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0109

Gnomad OTH AF: 0.0240

GnomAD4 exome AF: 0.0113 AC: 5151 AN: 456542 Hom.: 24 AF XY: 0.0109 AC XY: 2646 AN XY: 243636

African (AFR) AF: 0.0797 AC: 1021 AN: 12818

American (AMR) AF: 0.0107 AC: 258 AN: 24072

Ashkenazi Jewish (ASJ) AF: 0.00517 AC: 76 AN: 14714

East Asian (EAS) AF: 0.0000692 AC: 2 AN: 28888

South Asian (SAS) AF: 0.00619 AC: 309 AN: 49958

European-Finnish (FIN) AF: 0.00403 AC: 116 AN: 28818

Middle Eastern (MID) AF: 0.00808 AC: 17 AN: 2104

European-Non Finnish (NFE) AF: 0.0110 AC: 2961 AN: 269278

Other (OTH) AF: 0.0151 AC: 391 AN: 25892

GnomAD4 genome AF: 0.0319 AC: 4776 AN: 149782 Hom.: 167 Cov.: 0 AF XY: 0.0299 AC XY: 2182 AN XY: 73082

African (AFR) AF: 0.0893 AC: 3624 AN: 40602

American (AMR) AF: 0.0187 AC: 282 AN: 15042

Ashkenazi Jewish (ASJ) AF: 0.00579 AC: 20 AN: 3452

East Asian (EAS) AF: 0.000782 AC: 4 AN: 5118

South Asian (SAS) AF: 0.00573 AC: 27 AN: 4714

European-Finnish (FIN) AF: 0.00246 AC: 25 AN: 10182

Middle Eastern (MID) AF: 0.0240 AC: 7 AN: 292

European-Non Finnish (NFE) AF: 0.0110 AC: 739 AN: 67414

Other (OTH) AF: 0.0233 AC: 48 AN: 2062

Alfa AF: 0.00245 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 (auto)

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;