chr3-148994144-C-G

Variant names:

• chr3-148994144-C-G
• NM_004130.4:c.10C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004130.4(GYG1):​c.10C>G​(p.Gln4Glu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000137 in 1,460,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: GYG1 NM_004130.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.72

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2009947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYG1	NM_004130.4	c.10C>G	p.Gln4Glu	missense_variant, splice_region_variant	Exon 2 of 8	ENST00000345003.9	NP_004121.2
GYG1	NM_001184720.2	c.10C>G	p.Gln4Glu	missense_variant, splice_region_variant	Exon 2 of 7		NP_001171649.1
GYG1	NM_001184721.2	c.10C>G	p.Gln4Glu	missense_variant, splice_region_variant	Exon 2 of 6		NP_001171650.1
GYG1	XM_017006275.2	c.-34-2158C>G		intron_variant	Intron 1 of 5		XP_016861764.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GYG1	ENST00000345003.9	c.10C>G	p.Gln4Glu	missense_variant, splice_region_variant	Exon 2 of 8	1	NM_004130.4	ENSP00000340736.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460584 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726676

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.094	T;.;.;.;.;T
Eigen	Benign	-0.13
Eigen_PC	Benign	0.078
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.92	D;D;D;.;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T;T;T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.52	N;.;N;.;N;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.4	N;.;N;N;N;N
REVEL	Benign	0.099
Sift	Benign	0.59	T;.;T;T;T;T
Sift4G	Benign	0.92	T;T;T;T;T;T
Polyphen		0.81	P;B;B;B;.;.
Vest4		0.35
MutPred		0.41		Gain of disorder (P = 0.1058);Gain of disorder (P = 0.1058);Gain of disorder (P = 0.1058);Gain of disorder (P = 0.1058);Gain of disorder (P = 0.1058);Gain of disorder (P = 0.1058);
MVP		0.72
MPC		0.46
ClinPred		0.79	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.77
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-148711931;