13-95877706-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_020121.4(UGGT2):c.3379G>A(p.Ala1127Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 1 hom. )
Failed GnomAD Quality Control
Consequence
UGGT2
NM_020121.4 missense
NM_020121.4 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 7.16
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]
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ACMG classification
Classification made for transcript
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, 0.859
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UGGT2 | NM_020121.4 | c.3379G>A | p.Ala1127Thr | missense_variant | 28/39 | ENST00000376747.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UGGT2 | ENST00000376747.8 | c.3379G>A | p.Ala1127Thr | missense_variant | 28/39 | 1 | NM_020121.4 | P1 | |
UGGT2 | ENST00000463054.1 | n.689G>A | non_coding_transcript_exon_variant | 6/6 | 2 | ||||
UGGT2 | ENST00000491509.5 | n.654G>A | non_coding_transcript_exon_variant | 6/8 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249434Hom.: 1 AF XY: 0.0000297 AC XY: 4AN XY: 134718
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000274 AC: 4AN: 1459512Hom.: 1 Cov.: 31 AF XY: 0.00000551 AC XY: 4AN XY: 725866
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74342
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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 | Nov 02, 2023 | The c.3379G>A (p.A1127T) alteration is located in exon 28 (coding exon 28) of the UGGT2 gene. This alteration results from a G to A substitution at nucleotide position 3379, causing the alanine (A) at amino acid position 1127 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at F1132 (P = 0);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at