chr2-128113103-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020120.4(UGGT1):ā€‹c.541A>Gā€‹(p.Lys181Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000169 in 1,593,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000020 ( 0 hom., cov: 29)
Exomes š‘“: 0.000017 ( 0 hom. )

Consequence

UGGT1
NM_020120.4 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.15
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]

Genome browser will be placed here

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=0.23523244).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UGGT1NM_020120.4 linkuse as main transcriptc.541A>G p.Lys181Glu missense_variant 6/41 ENST00000259253.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UGGT1ENST00000259253.11 linkuse as main transcriptc.541A>G p.Lys181Glu missense_variant 6/411 NM_020120.4 P1Q9NYU2-1
UGGT1ENST00000376723.7 linkuse as main transcriptc.*581A>G 3_prime_UTR_variant, NMD_transcript_variant 6/411
UGGT1ENST00000438277.5 linkuse as main transcriptc.*129A>G 3_prime_UTR_variant, NMD_transcript_variant 4/261

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000576
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000458
AC:
11
AN:
239916
Hom.:
0
AF XY:
0.0000231
AC XY:
3
AN XY:
129790
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000720
Gnomad EAS exome
AF:
0.000225
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000166
AC:
24
AN:
1441770
Hom.:
0
Cov.:
29
AF XY:
0.0000126
AC XY:
9
AN XY:
716084
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000241
Gnomad4 ASJ exome
AF:
0.000508
Gnomad4 EAS exome
AF:
0.000128
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000182
Gnomad4 OTH exome
AF:
0.0000504
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152184
Hom.:
0
Cov.:
29
AF XY:
0.0000269
AC XY:
2
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000576
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000900
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000494
AC:
6

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 submitterclinical testingAmbry GeneticsJun 29, 2022The c.541A>G (p.K181E) alteration is located in exon 6 (coding exon 6) of the UGGT1 gene. This alteration results from a A to G substitution at nucleotide position 541, causing the lysine (K) at amino acid position 181 to be replaced by a glutamic acid (E). 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
0.17
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.19
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.039
T
Eigen
Benign
-0.090
Eigen_PC
Benign
0.12
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.81
T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.23
Sift
Benign
0.12
T
Sift4G
Benign
0.51
T
Polyphen
0.083
B
Vest4
0.70
MutPred
0.38
Loss of methylation at K181 (P = 0.0021);
MVP
0.37
MPC
0.087
ClinPred
0.15
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.33
gMVP
0.74

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.

Other links and lift over

dbSNP: rs767223317; hg19: chr2-128870677; API