chrX-2830140-C-T

Variant names:

• chrX-2830140-C-T
• rs368700751
• NM_001079855.2:c.-49C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001079855.2(GYG2):​c.-49C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,188,678 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 232 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00050 (0 hom., 14 hem., cov: 24)
  • Exomes 𝑓: 0.00069 (0 hom. 218 hem.)
• Consequence: GYG2 NM_001079855.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.964
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-2830140-C-T is Benign according to our data. Variant chrX-2830140-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 516935.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 14 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001079855.2. 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.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	NP_001073324.1	O15488-2
	GYG2	NM_001079855.2	MANE Select	c.-49C>T		5_prime_UTR	Exon 2 of 11	NP_001073324.1	O15488-2
	GYG2	NM_003918.3		c.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	NP_003909.2	O15488-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GYG2	ENST00000398806.8	TSL:1 MANE Select	c.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000381786.3	O15488-2
	GYG2	ENST00000381163.7	TSL:1	c.-49C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 12	ENSP00000370555.3	O15488-1
	GYG2	ENST00000398806.8	TSL:1 MANE Select	c.-49C>T		5_prime_UTR	Exon 2 of 11	ENSP00000381786.3	O15488-2

Frequencies

GnomAD3 genomes AF: 0.000497 AC: 56 AN: 112709 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000186

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000883

Gnomad OTH AF: 0.000662

GnomAD2 exomes AF: 0.000324 AC: 57 AN: 175926 AF XY: 0.000241

Gnomad AFR exome AF: 0.0000785

Gnomad AMR exome AF: 0.0000373

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000694

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000693 AC: 746 AN: 1075969 Hom.: 0 Cov.: 26 AF XY: 0.000631 AC XY: 218 AN XY: 345247

African (AFR) AF: 0.000192 AC: 5 AN: 25987

American (AMR) AF: 0.0000286 AC: 1 AN: 34975

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19130

East Asian (EAS) AF: 0.0000333 AC: 1 AN: 30031

South Asian (SAS) AF: 0.0000187 AC: 1 AN: 53347

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40347

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4070

European-Non Finnish (NFE) AF: 0.000862 AC: 709 AN: 822774

Other (OTH) AF: 0.000640 AC: 29 AN: 45308

GnomAD4 genome AF: 0.000497 AC: 56 AN: 112709 Hom.: 0 Cov.: 24 AF XY: 0.000401 AC XY: 14 AN XY: 34883

African (AFR) AF: 0.000193 AC: 6 AN: 31062

American (AMR) AF: 0.000186 AC: 2 AN: 10775

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2658

East Asian (EAS) AF: 0.00 AC: 0 AN: 3547

South Asian (SAS) AF: 0.00 AC: 0 AN: 2745

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6249

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 240

European-Non Finnish (NFE) AF: 0.000883 AC: 47 AN: 53237

Other (OTH) AF: 0.000662 AC: 1 AN: 1511

Alfa AF: 0.000781 Hom.: 6

Bravo AF: 0.000446

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.8
DANN	Benign	0.87
PhyloP100		-0.96
PromoterAI		-0.0042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism

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: rs368700751; hg19: chrX-2748181;