13-95859624-C-G

Variant names:

• chr13-95859624-C-G
• NM_020121.4:c.3792G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020121.4(UGGT2):​c.3792G>C​(p.Trp1264Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGGT2 NM_020121.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.69

Genes affected

UGGT2 (HGNC:15664): (UDP-glucose glycoprotein glucosyltransferase 2) 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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGGT2	NM_020121.4	c.3792G>C	p.Trp1264Cys	missense_variant	Exon 33 of 39	ENST00000376747.8	NP_064506.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGGT2	ENST00000376747.8	c.3792G>C	p.Trp1264Cys	missense_variant	Exon 33 of 39	1	NM_020121.4	ENSP00000365938.3
UGGT2	ENST00000462472.1	n.272G>C		non_coding_transcript_exon_variant	Exon 1 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 16, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3792G>C (p.W1264C) alteration is located in exon 33 (coding exon 33) of the UGGT2 gene. This alteration results from a G to C substitution at nucleotide position 3792, causing the tryptophan (W) at amino acid position 1264 to be replaced by a cysteine (C). 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	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.52	D
Eigen	Pathogenic	0.90
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.063	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Pathogenic	3.7	H
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-13	D
REVEL	Uncertain	0.64
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.98
MutPred		0.71		Gain of catalytic residue at L1265 (P = 0);
MVP		0.53
MPC		0.44
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.95
gMVP		0.89

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-96511878;