rs191178836

Variant names:

• chr3-148991479-A-G
• rs191178836
• ENST00000296048.10:c.-162A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000296048.10(GYG1):​c.-162A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 870,080 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0063 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00072 (5 hom.)
• Consequence: GYG1 ENST00000296048.10 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.62
• Publications: 0 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, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics
• glycogen storage disease XV

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 3-148991479-A-G is Benign according to our data. Variant chr3-148991479-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1189350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00629 (958/152230) while in subpopulation AFR AF = 0.0218 (908/41564). AF 95% confidence interval is 0.0207. There are 6 homozygotes in GnomAd4. There are 441 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000296048.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	NM_004130.4	MANE Select	c.-162A>G		upstream_gene	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.-162A>G		upstream_gene	N/A	NP_001171649.1	P46976-2
	GYG1	NM_001184721.2		c.-162A>G		upstream_gene	N/A	NP_001171650.1	P46976-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	ENST00000296048.10	TSL:1	c.-162A>G		5_prime_UTR	Exon 1 of 7	ENSP00000296048.6	P46976-2
	GYG1	ENST00000627418.2	TSL:5	c.-162A>G		5_prime_UTR	Exon 1 of 6	ENSP00000486061.1	G5E9W8
	GYG1	ENST00000942925.1		c.-162A>G		5_prime_UTR	Exon 1 of 4	ENSP00000612984.1

Frequencies

GnomAD3 genomes AF: 0.00628 AC: 956 AN: 152122 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0219

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00641

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000717 AC: 515 AN: 717850 Hom.: 5 Cov.: 9 AF XY: 0.000595 AC XY: 223 AN XY: 374550

African (AFR) AF: 0.0223 AC: 334 AN: 14996

American (AMR) AF: 0.00245 AC: 72 AN: 29384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19434

East Asian (EAS) AF: 0.00 AC: 0 AN: 27506

South Asian (SAS) AF: 0.0000485 AC: 3 AN: 61820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32770

Middle Eastern (MID) AF: 0.000724 AC: 2 AN: 2764

European-Non Finnish (NFE) AF: 0.0000810 AC: 40 AN: 494062

Other (OTH) AF: 0.00182 AC: 64 AN: 35114

GnomAD4 genome AF: 0.00629 AC: 958 AN: 152230 Hom.: 6 Cov.: 33 AF XY: 0.00592 AC XY: 441 AN XY: 74444

African (AFR) AF: 0.0218 AC: 908 AN: 41564

American (AMR) AF: 0.00235 AC: 36 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00690 AC: 2 AN: 290

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 67966

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00465 Hom.: 0

Bravo AF: 0.00719

Asia WGS AF: 0.00145 AC: 5 AN: 3466

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	9.6
DANN	Benign	0.65
PhyloP100		-1.6
PromoterAI		-0.075	Neutral
Mutation Taster		=300/0	polymorphism

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: rs191178836; hg19: chr3-148709266;