rs1436973888

Variant names:

• chr13-95859625-C-G
• rs1436973888
• NM_020121.4:c.3791G>C
• UGGT2 p.Trp1264Ser

Your query was ambiguous. Multiple possible variants found:

• chr13-95859625-C-G
• chr13-95859625-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_020121.4(UGGT2):​c.3791G>C​(p.Trp1264Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,609,964 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. W1264C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: UGGT2 NM_020121.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.40
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.95

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.3791G>C	p.Trp1264Ser	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.3791G>C	p.Trp1264Ser	missense	Exon 33 of 39	ENSP00000365938.3	Q9NYU1-1
	UGGT2	ENST00000943424.1		c.3872G>C	p.Trp1291Ser	missense	Exon 34 of 40	ENSP00000613483.1
	UGGT2	ENST00000943423.1		c.3824G>C	p.Trp1275Ser	missense	Exon 34 of 40	ENSP00000613482.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151910 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000412 AC: 6 AN: 1458054 Hom.: 0 Cov.: 30 AF XY: 0.00000552 AC XY: 4 AN XY: 725276

African (AFR) AF: 0.00 AC: 0 AN: 33332

American (AMR) AF: 0.00 AC: 0 AN: 44282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26004

East Asian (EAS) AF: 0.00 AC: 0 AN: 39466

South Asian (SAS) AF: 0.00 AC: 0 AN: 85742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00000541 AC: 6 AN: 1110048

Other (OTH) AF: 0.00 AC: 0 AN: 60174

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151910 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74168

African (AFR) AF: 0.00 AC: 0 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67942

Other (OTH) AF: 0.00 AC: 0 AN: 2084

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	1.0
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Pathogenic	1.0	D
M_CAP	Benign	0.050	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		7.4
PrimateAI	Pathogenic	0.80	T
PROVEAN	Pathogenic	-14	D
REVEL	Uncertain	0.59
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Varity_R		0.96
gMVP		0.87
Mutation Taster		=18/82	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1436973888; hg19: chr13-96511879;