2-128135634-T-C

Variant names:

• chr2-128135634-T-C
• rs7577867
• NM_020120.4:c.1583+673T>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.1583+673T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 151,980 control chromosomes in the GnomAD database, including 14,497 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 0.43 (14497 hom., cov: 33)
• Consequence: UGGT1 NM_020120.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449
• 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=-0.87).
• 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.1583+673T>C		intron_variant	Intron 15 of 40	ENST00000259253.11	NP_064505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGGT1	ENST00000259253.11	c.1583+673T>C		intron_variant	Intron 15 of 40	1	NM_020120.4	ENSP00000259253.6
UGGT1	ENST00000376723.7	n.*1623+673T>C		intron_variant	Intron 15 of 40	1		ENSP00000365913.3
UGGT1	ENST00000438277.5	n.*1171+673T>C		intron_variant	Intron 13 of 25	1		ENSP00000392701.1

Frequencies

GnomAD3 genomes AF: 0.432 AC: 65610 AN: 151862 Hom.: 14488 Cov.: 33

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.650

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.405

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.432 AC: 65655 AN: 151980 Hom.: 14497 Cov.: 33 AF XY: 0.433 AC XY: 32167 AN XY: 74298

African (AFR) AF: 0.434 AC: 17981 AN: 41428

American (AMR) AF: 0.528 AC: 8059 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1542 AN: 3472

East Asian (EAS) AF: 0.651 AC: 3360 AN: 5164

South Asian (SAS) AF: 0.349 AC: 1682 AN: 4820

European-Finnish (FIN) AF: 0.383 AC: 4051 AN: 10564

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

European-Non Finnish (NFE) AF: 0.405 AC: 27528 AN: 67950

Other (OTH) AF: 0.456 AC: 965 AN: 2114

Alfa AF: 0.413 Hom.: 8439

Bravo AF: 0.448

Asia WGS AF: 0.417 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.74
DANN	Benign	0.52
PhyloP100		-0.45
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: rs7577867; hg19: chr2-128893208;