Genetic Variant UGGT1:p.Pro175Ala (chr2-128113085-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020120.4(UGGT1):c.523C>G(p.Pro175Ala) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P175S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UGGT1
NM_020120.4 missense, splice_region

Scores

Splicing: ADA: 0.8895

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.18

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

disorder of protein N-glycosylation
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

UGGT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2706757).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGGT1	NM_020120.4 link	c.523C>G	p.Pro175Ala	missense_variant, splice_region_variant	Exon 6 of 41	ENST00000259253.11	NP_064505.1	Q9NYU2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGGT1	ENST00000259253.11 link	c.523C>G	p.Pro175Ala	missense_variant, splice_region_variant	Exon 6 of 41	1	NM_020120.4	ENSP00000259253.6		Q9NYU2-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1330404

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

654116

African (AFR)

AF:

0.00

AC:

AN:

28952

American (AMR)

AF:

0.00

AC:

AN:

28282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22042

East Asian (EAS)

AF:

0.00

AC:

AN:

35364

South Asian (SAS)

AF:

0.00

AC:

AN:

64776

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5246

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1041740

Other (OTH)

AF:

0.00

AC:

AN:

53952

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.16

Eigen

Benign

0.022

Eigen_PC

Benign

0.20

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.020

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.5

PhyloP100

5.2

PrimateAI

Benign

0.47

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.12

Sift

Benign

0.21

Sift4G

Benign

0.19

Polyphen

0.15

Vest4

0.34

MutPred

0.26

Loss of glycosylation at P175 (P = 0.0331);

MVP

0.44

MPC

0.083

ClinPred

0.94

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.38

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.89

dbscSNV1_RF

Benign

0.66

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over