NM_004130.4:c.7+10C>G

Variant names:

• chr3-148991657-C-G
• rs771870422
• NM_004130.4:c.7+10C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004130.4(GYG1):​c.7+10C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000727 in 1,376,082 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: GYG1 NM_004130.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.18
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	NM_004130.4	MANE Select	c.7+10C>G		intron	N/A	NP_004121.2
	GYG1	NM_001184720.2		c.7+10C>G		intron	N/A	NP_001171649.1	P46976-2
	GYG1	NM_001184721.2		c.7+10C>G		intron	N/A	NP_001171650.1	P46976-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG1	ENST00000345003.9	TSL:1 MANE Select	c.7+10C>G		intron	N/A	ENSP00000340736.4	P46976-1
	GYG1	ENST00000296048.10	TSL:1	c.7+10C>G		intron	N/A	ENSP00000296048.6	P46976-2
	GYG1	ENST00000484197.5	TSL:1	c.7+10C>G		intron	N/A	ENSP00000420683.1	P46976-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000789 AC: 1 AN: 126744 AF XY: 0.0000143

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000128

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.27e-7 AC: 1 AN: 1376082 Hom.: 0 Cov.: 30 AF XY: 0.00000147 AC XY: 1 AN XY: 679650

African (AFR) AF: 0.00 AC: 0 AN: 30038

American (AMR) AF: 0.00 AC: 0 AN: 36010

Ashkenazi Jewish (ASJ) AF: 0.0000403 AC: 1 AN: 24826

East Asian (EAS) AF: 0.00 AC: 0 AN: 35008

South Asian (SAS) AF: 0.00 AC: 0 AN: 78706

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076276

Other (OTH) AF: 0.00 AC: 0 AN: 57396

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000436 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.91
PhyloP100		1.2
PromoterAI		-0.099	Neutral

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: rs771870422; hg19: chr3-148709444;