rs744265

Variant names:

• chr2-128186850-T-C
• rs744265
• NM_020120.4:c.4476+51T>C

Variant summary

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

The NM_020120.4(UGGT1):​c.4476+51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.586 in 1,248,680 control chromosomes in the GnomAD database, including 217,164 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 0.57 (25237 hom., cov: 30)
  • Exomes 𝑓: 0.59 (191927 hom.)
• Consequence: UGGT1 NM_020120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190
• Publications: 9 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 (SAS) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020120.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGGT1	NM_020120.4	MANE Select	c.4476+51T>C		intron	N/A	NP_064505.1
	UGGT1	NR_027671.3		n.4815+51T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGGT1	ENST00000259253.11	TSL:1 MANE Select	c.4476+51T>C		intron	N/A	ENSP00000259253.6
	UGGT1	ENST00000376723.7	TSL:1	n.*4516+51T>C		intron	N/A	ENSP00000365913.3
	UGGT1	ENST00000418197.1	TSL:5	c.201+51T>C		intron	N/A	ENSP00000389441.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 86853 AN: 151536 Hom.: 25215 Cov.: 30

Gnomad AFR AF: 0.584

Gnomad AMI AF: 0.625

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.651

Gnomad FIN AF: 0.616

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.595

Gnomad OTH AF: 0.542

GnomAD2 exomes AF: 0.567 AC: 114193 AN: 201332 AF XY: 0.573

Gnomad AFR exome AF: 0.584

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.558

Gnomad EAS exome AF: 0.341

Gnomad FIN exome AF: 0.616

Gnomad NFE exome AF: 0.594

Gnomad OTH exome AF: 0.576

GnomAD4 exome AF: 0.587 AC: 644429 AN: 1097026 Hom.: 191927 Cov.: 13 AF XY: 0.589 AC XY: 325890 AN XY: 553632

African (AFR) AF: 0.585 AC: 14007 AN: 23952

American (AMR) AF: 0.457 AC: 13651 AN: 29846

Ashkenazi Jewish (ASJ) AF: 0.557 AC: 11718 AN: 21054

East Asian (EAS) AF: 0.359 AC: 12708 AN: 35446

South Asian (SAS) AF: 0.642 AC: 41830 AN: 65194

European-Finnish (FIN) AF: 0.620 AC: 31243 AN: 50356

Middle Eastern (MID) AF: 0.473 AC: 2301 AN: 4860

European-Non Finnish (NFE) AF: 0.598 AC: 489990 AN: 819604

Other (OTH) AF: 0.578 AC: 26981 AN: 46714

GnomAD4 genome AF: 0.573 AC: 86926 AN: 151654 Hom.: 25237 Cov.: 30 AF XY: 0.572 AC XY: 42378 AN XY: 74106

African (AFR) AF: 0.584 AC: 24112 AN: 41292

American (AMR) AF: 0.475 AC: 7231 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1928 AN: 3468

East Asian (EAS) AF: 0.347 AC: 1791 AN: 5154

South Asian (SAS) AF: 0.652 AC: 3123 AN: 4792

European-Finnish (FIN) AF: 0.616 AC: 6454 AN: 10484

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.595 AC: 40415 AN: 67912

Other (OTH) AF: 0.547 AC: 1153 AN: 2108

Alfa AF: 0.575 Hom.: 48927

Bravo AF: 0.559

Asia WGS AF: 0.582 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.31
PhyloP100		-0.19
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: rs744265; hg19: chr2-128944424; COSMIC: COSV52141334; COSMIC: COSV52141334;