3-148991537-G-A

Position:

• chr3-148991537-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000296048.10(GYG1):​c.-104G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00308 in 1,439,246 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (80 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (54 hom.)
• Consequence: GYG1 ENST00000296048.10 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.734

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-148991537-G-A is Benign according to our data. Variant chr3-148991537-G-A is described in ClinVar as [Benign]. Clinvar id is 1260828.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0524 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GYG1	NM_004130.4			upstream_gene_variant		ENST00000345003.9	NP_004121.2
GYG1	NM_001184720.2			upstream_gene_variant			NP_001171649.1
GYG1	NM_001184721.2			upstream_gene_variant			NP_001171650.1
GYG1	XM_017006275.2			upstream_gene_variant			XP_016861764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYG1	ENST00000345003.9			upstream_gene_variant		1	NM_004130.4	ENSP00000340736

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2411 AN: 152164 Hom.: 78 Cov.: 33

Gnomad AFR AF: 0.0541

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00824

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.00156 AC: 2014 AN: 1286974 Hom.: 54 Cov.: 19 AF XY: 0.00128 AC XY: 821 AN XY: 639996

Gnomad4 AFR exome AF: 0.0512

Gnomad4 AMR exome AF: 0.00447

Gnomad4 ASJ exome AF: 0.000123

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000182

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000126

Gnomad4 OTH exome AF: 0.00448

GnomAD4 genome AF: 0.0159 AC: 2422 AN: 152272 Hom.: 80 Cov.: 33 AF XY: 0.0160 AC XY: 1192 AN XY: 74450

Gnomad4 AFR AF: 0.0542

Gnomad4 AMR AF: 0.00823

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.0128 Hom.: 8

Bravo AF: 0.0183

Asia WGS AF: 0.00580 AC: 20 AN: 3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.1
DANN	Benign	0.89

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: rs149443762; hg19: chr3-148709324;