ENST00000381163.7:c.42C>T

Variant names:

• chrX-2843032-C-T
• rs765257386
• ENST00000381163.7:c.42C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The ENST00000381163.7(GYG2):​c.42C>T​(p.Leu14Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000051 in 392,096 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L14L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000051 (0 hom. 1 hem.)
• Consequence: GYG2 ENST00000381163.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.608
• Publications: 0 publications found

Genes affected

GYG2 (HGNC:4700): (glycogenin 2) This gene encodes a member of the the glycogenin family. Glycogenin is a self-glucosylating protein involved in the initiation reactions of glycogen biosynthesis. A gene on chromosome 3 encodes the muscle glycogenin and this X-linked gene encodes the glycogenin mainly present in liver; both are involved in blood glucose homeostasis. This gene has a short version on chromosome Y, which is 3' truncated and can not make a functional protein. Multiple alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=-0.608 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000381163.7. 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
	GYG2	NM_001079855.2	MANE Select	c.8-181C>T		intron	N/A	NP_001073324.1	O15488-2
	GYG2	NM_003918.3		c.42C>T	p.Leu14Leu	synonymous	Exon 3 of 12	NP_003909.2	O15488-1
	GYG2	NM_001184703.2		c.42C>T	p.Leu14Leu	synonymous	Exon 3 of 10	NP_001171632.1	O15488-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG2	ENST00000381163.7	TSL:1	c.42C>T	p.Leu14Leu	synonymous	Exon 3 of 12	ENSP00000370555.3	O15488-1
	GYG2	ENST00000398806.8	TSL:1 MANE Select	c.8-181C>T		intron	N/A	ENSP00000381786.3	O15488-2
	GYG2	ENST00000958345.1		c.42C>T	p.Leu14Leu	synonymous	Exon 3 of 12	ENSP00000628404.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000510 AC: 2 AN: 392096 Hom.: 0 Cov.: 4 AF XY: 0.00000724 AC XY: 1 AN XY: 138094

African (AFR) AF: 0.00 AC: 0 AN: 12249

American (AMR) AF: 0.00 AC: 0 AN: 26256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14014

East Asian (EAS) AF: 0.0000430 AC: 1 AN: 23259

South Asian (SAS) AF: 0.00 AC: 0 AN: 36029

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28328

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2323

European-Non Finnish (NFE) AF: 0.00000440 AC: 1 AN: 227225

Other (OTH) AF: 0.00 AC: 0 AN: 22413

GnomAD4 genome Cov.: 22

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.70
DANN	Benign	0.62
PhyloP100		-0.61
PromoterAI		0.010	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs765257386; hg19: chrX-2761073;