Variant 2-128133145-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020120.4(UGGT1):c.1382T>C(p.Val461Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000115 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

UGGT1
NM_020120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.85

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1431301).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UGGT1	NM_020120.4 linkuse as main transcript	c.1382T>C	p.Val461Ala	missense_variant	14/41	ENST00000259253.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGGT1	ENST00000259253.11 linkuse as main transcript	c.1382T>C	p.Val461Ala	missense_variant	14/41	1	NM_020120.4	P1	Q9NYU2-1
UGGT1	ENST00000376723.7 linkuse as main transcript	c.*1422T>C		3_prime_UTR_variant, NMD_transcript_variant	14/41	1
UGGT1	ENST00000438277.5 linkuse as main transcript	c.*970T>C		3_prime_UTR_variant, NMD_transcript_variant	12/26	1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000796

AC:

AN:

251378

Hom.:

AF XY:

0.0000736

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000120

AC:

176

AN:

1461642

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000117

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000988

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.1382T>C (p.V461A) alteration is located in exon 14 (coding exon 14) of the UGGT1 gene. This alteration results from a T to C substitution at nucleotide position 1382, causing the valine (V) at amino acid position 461 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.31

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.44

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.022

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.66

M_CAP

Benign

0.010

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.88

D;D

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.13

Sift

Benign

0.065

Sift4G

Uncertain

0.046

Polyphen

0.060

Vest4

0.43

MVP

0.68

MPC

0.080

ClinPred

0.13

GERP RS

4.4

Varity_R

0.18

gMVP

0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over