chr2-128133493-C-T

Variant names:

• chr2-128133493-C-T
• rs11903649
• NM_020120.4:c.1497+233C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020120.4(UGGT1):​c.1497+233C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 151,972 control chromosomes in the GnomAD database, including 14,041 homozygotes. 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: 𝑓 0.42 (14041 hom., cov: 32)
• Consequence: UGGT1 NM_020120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547
• Publications: 6 publications found

Genes affected

UGGT1 (HGNC:15663): (UDP-glucose glycoprotein glucosyltransferase 1) UDP-glucose:glycoprotein glucosyltransferase (UGT) is a soluble protein of the endoplasmic reticulum (ER) that selectively reglucosylates unfolded glycoproteins, thus providing quality control for protein transport out of the ER.[supplied by OMIM, Oct 2009]

UGGT1 Gene-Disease associations (from GenCC):

• disorder of protein N-glycosylation

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGGT1	NM_020120.4	c.1497+233C>T		intron_variant	Intron 14 of 40	ENST00000259253.11	NP_064505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGGT1	ENST00000259253.11	c.1497+233C>T		intron_variant	Intron 14 of 40	1	NM_020120.4	ENSP00000259253.6
UGGT1	ENST00000376723.7	n.*1537+233C>T		intron_variant	Intron 14 of 40	1		ENSP00000365913.3
UGGT1	ENST00000438277.5	n.*1085+233C>T		intron_variant	Intron 12 of 25	1		ENSP00000392701.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64519 AN: 151854 Hom.: 14036 Cov.: 32

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.425 AC: 64550 AN: 151972 Hom.: 14041 Cov.: 32 AF XY: 0.426 AC XY: 31623 AN XY: 74262

African (AFR) AF: 0.409 AC: 16950 AN: 41410

American (AMR) AF: 0.525 AC: 8027 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3367 AN: 5176

South Asian (SAS) AF: 0.349 AC: 1676 AN: 4806

European-Finnish (FIN) AF: 0.382 AC: 4036 AN: 10552

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.405 AC: 27514 AN: 67958

Other (OTH) AF: 0.451 AC: 953 AN: 2114

Alfa AF: 0.415 Hom.: 22710

Bravo AF: 0.440

Asia WGS AF: 0.417 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.41
PhyloP100		-0.55
Mutation Taster		=100/0	polymorphism (auto)

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: rs11903649; hg19: chr2-128891067; COSMIC: COSV52141456;