Variant chr2-128129099-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.1297T>C(p.Ser433Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UGGT1
NM_020120.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

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:

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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=0.24116877).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGGT1	NM_020120.4 linkuse as main transcript	c.1297T>C	p.Ser433Pro	missense_variant	13/41	ENST00000259253.11	NP_064505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGGT1	ENST00000259253.11 linkuse as main transcript	c.1297T>C	p.Ser433Pro	missense_variant	13/41	1	NM_020120.4	ENSP00000259253	P1	Q9NYU2-1
UGGT1	ENST00000376723.7 linkuse as main transcript	c.*1337T>C		3_prime_UTR_variant, NMD_transcript_variant	13/41	1		ENSP00000365913
UGGT1	ENST00000438277.5 linkuse as main transcript	c.*885T>C		3_prime_UTR_variant, NMD_transcript_variant	11/26	1		ENSP00000392701

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

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

Jun 02, 2023

The c.1297T>C (p.S433P) alteration is located in exon 13 (coding exon 13) of the UGGT1 gene. This alteration results from a T to C substitution at nucleotide position 1297, causing the serine (S) at amino acid position 433 to be replaced by a proline (P). 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

0.13

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.80

M_CAP

Benign

0.011

MetaRNN

Benign

0.24

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Benign

0.28

Sift4G

Benign

0.33

Polyphen

0.72

Vest4

0.26

MVP

0.69

MPC

0.16

ClinPred

0.48

GERP RS

1.6

Varity_R

0.18

gMVP

0.83

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