3-148997054-TTGTGTGTGTGTGTG-TTGTGTGTGTGTG

Variant names:

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

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+179delGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 595,546 control chromosomes in the GnomAD database, including 7,736 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (4893 hom., cov: 0)
  • Exomes 𝑓: 0.23 (2843 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-TTG-T is Benign according to our data. Variant chr3-148997054-TTG-T is described in ClinVar as Benign. ClinVar VariationId is 1240865.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 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+179delGT		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.481+178_481+179delGT		intron	N/A	NP_001171649.1
	GYG1	NM_001184721.2		c.481+178_481+179delGT		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+152delTG		intron	N/A	ENSP00000340736.4
	GYG1	ENST00000296048.10	TSL:1	c.481+151_481+152delTG		intron	N/A	ENSP00000296048.6
	GYG1	ENST00000484197.5	TSL:1	c.481+151_481+152delTG		intron	N/A	ENSP00000420683.1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 37945 AN: 149440 Hom.: 4890 Cov.: 0

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.346

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.270

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.231 AC: 102927 AN: 445990 Hom.: 2843 AF XY: 0.228 AC XY: 54222 AN XY: 238066

African (AFR) AF: 0.231 AC: 2952 AN: 12758

American (AMR) AF: 0.242 AC: 5746 AN: 23792

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 3350 AN: 14420

East Asian (EAS) AF: 0.359 AC: 10178 AN: 28328

South Asian (SAS) AF: 0.203 AC: 9919 AN: 48748

European-Finnish (FIN) AF: 0.188 AC: 5268 AN: 28054

Middle Eastern (MID) AF: 0.276 AC: 571 AN: 2066

European-Non Finnish (NFE) AF: 0.224 AC: 58818 AN: 262502

Other (OTH) AF: 0.242 AC: 6125 AN: 25322

GnomAD4 genome AF: 0.254 AC: 37980 AN: 149556 Hom.: 4893 Cov.: 0 AF XY: 0.255 AC XY: 18584 AN XY: 72968

African (AFR) AF: 0.274 AC: 11107 AN: 40562

American (AMR) AF: 0.309 AC: 4648 AN: 15020

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 931 AN: 3448

East Asian (EAS) AF: 0.399 AC: 2040 AN: 5112

South Asian (SAS) AF: 0.216 AC: 1016 AN: 4712

European-Finnish (FIN) AF: 0.179 AC: 1812 AN: 10124

Middle Eastern (MID) AF: 0.312 AC: 91 AN: 292

European-Non Finnish (NFE) AF: 0.229 AC: 15434 AN: 67326

Other (OTH) AF: 0.286 AC: 588 AN: 2056

Alfa AF: 0.174 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

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;