rs148619511

Positions:

• chr3-148996317-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004130.4(GYG1):​c.159A>G​(p.Thr53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 1,610,978 control chromosomes in the GnomAD database, including 158 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0076 (11 hom., cov: 32)
  • Exomes 𝑓: 0.012 (147 hom.)
• Consequence: GYG1 NM_004130.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.533

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-148996317-A-G is Benign according to our data. Variant chr3-148996317-A-G is described in ClinVar as [Benign]. Clinvar id is 380453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.533 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00763 (1162/152364) while in subpopulation NFE AF= 0.0129 (879/68034). AF 95% confidence interval is 0.0122. There are 11 homozygotes in gnomad4. There are 515 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GYG1	NM_004130.4	c.159A>G	p.Thr53=	synonymous_variant	3/8	ENST00000345003.9
GYG1	NM_001184720.2	c.159A>G	p.Thr53=	synonymous_variant	3/7
GYG1	NM_001184721.2	c.159A>G	p.Thr53=	synonymous_variant	3/6
GYG1	XM_017006275.2	c.-19A>G		5_prime_UTR_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYG1	ENST00000345003.9	c.159A>G	p.Thr53=	synonymous_variant	3/8	1	NM_004130.4

Frequencies

GnomAD3 genomes AF: 0.00763 AC: 1162 AN: 152246 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00778

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00320

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00813

GnomAD3 exomes AF: 0.00723 AC: 1817 AN: 251224 Hom.: 13 AF XY: 0.00683 AC XY: 927 AN XY: 135776

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.00520

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.000109

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00434

Gnomad NFE exome AF: 0.0124

Gnomad OTH exome AF: 0.00766

GnomAD4 exome AF: 0.0121 AC: 17690 AN: 1458614 Hom.: 147 Cov.: 31 AF XY: 0.0118 AC XY: 8562 AN XY: 725684

Gnomad4 AFR exome AF: 0.00207

Gnomad4 AMR exome AF: 0.00559

Gnomad4 ASJ exome AF: 0.00295

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00470

Gnomad4 NFE exome AF: 0.0148

Gnomad4 OTH exome AF: 0.0102

GnomAD4 genome AF: 0.00763 AC: 1162 AN: 152364 Hom.: 11 Cov.: 32 AF XY: 0.00691 AC XY: 515 AN XY: 74526

Gnomad4 AFR AF: 0.00240

Gnomad4 AMR AF: 0.00777

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00320

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00956 Hom.: 6

Bravo AF: 0.00787

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0108

EpiControl AF: 0.0117

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jun 29, 2023	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	GYG1: BP4, BP7, BS1, BS2 -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 05, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Glycogen storage disease XV;C4015452:Polyglucosan body myopathy type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs148619511; hg19: chr3-148714104;