chr13-95859624-C-A

Variant names:

• chr13-95859624-C-A
• rs755219228
• NM_020121.4:c.3792G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020121.4(UGGT2):​c.3792G>T​(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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UGGT2 NM_020121.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.69
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020121.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGGT2	NM_020121.4	MANE Select	c.3792G>T	p.Trp1264Cys	missense	Exon 33 of 39	NP_064506.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGGT2	ENST00000376747.8	TSL:1 MANE Select	c.3792G>T	p.Trp1264Cys	missense	Exon 33 of 39	ENSP00000365938.3	Q9NYU1-1
	UGGT2	ENST00000943424.1		c.3873G>T	p.Trp1291Cys	missense	Exon 34 of 40	ENSP00000613483.1
	UGGT2	ENST00000943423.1		c.3825G>T	p.Trp1275Cys	missense	Exon 34 of 40	ENSP00000613482.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1458042 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725258

African (AFR) AF: 0.00 AC: 0 AN: 33322

American (AMR) AF: 0.00 AC: 0 AN: 44304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26000

East Asian (EAS) AF: 0.00 AC: 0 AN: 39468

South Asian (SAS) AF: 0.00 AC: 0 AN: 85726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110034

Other (OTH) AF: 0.00 AC: 0 AN: 60182

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	30
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	0.068	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		5.7
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
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs755219228; hg19: chr13-96511878;