4-68929908-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024743.4(UGT2A3):​c.1489G>A​(p.Ala497Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.823 in 1,612,308 control chromosomes in the GnomAD database, including 554,678 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 42135 hom., cov: 31)
Exomes 𝑓: 0.83 ( 512543 hom. )

Consequence

UGT2A3
NM_024743.4 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.277

Publications

16 publications found
Variant links:
Genes affected
UGT2A3 (HGNC:28528): (UDP glucuronosyltransferase family 2 member A3) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=1.3052224E-6).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.852 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UGT2A3NM_024743.4 linkc.1489G>A p.Ala497Thr missense_variant Exon 6 of 6 ENST00000251566.9 NP_079019.3 Q6UWM9
UGT2A3XM_011532247.3 linkc.1507G>A p.Ala503Thr missense_variant Exon 6 of 6 XP_011530549.1
UGT2A3XM_047416177.1 linkc.622G>A p.Ala208Thr missense_variant Exon 6 of 6 XP_047272133.1
UGT2A3NR_024010.2 linkn.1630G>A non_coding_transcript_exon_variant Exon 7 of 7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UGT2A3ENST00000251566.9 linkc.1489G>A p.Ala497Thr missense_variant Exon 6 of 6 1 NM_024743.4 ENSP00000251566.4 Q6UWM9
UGT2A3ENST00000503012.1 linkn.*665G>A non_coding_transcript_exon_variant Exon 7 of 7 2 ENSP00000424092.1 D6RBL8
UGT2A3ENST00000503012.1 linkn.*665G>A 3_prime_UTR_variant Exon 7 of 7 2 ENSP00000424092.1 D6RBL8

Frequencies

GnomAD3 genomes
AF:
0.731
AC:
110912
AN:
151770
Hom.:
42124
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.531
Gnomad AMI
AF:
0.830
Gnomad AMR
AF:
0.660
Gnomad ASJ
AF:
0.856
Gnomad EAS
AF:
0.677
Gnomad SAS
AF:
0.802
Gnomad FIN
AF:
0.740
Gnomad MID
AF:
0.744
Gnomad NFE
AF:
0.858
Gnomad OTH
AF:
0.736
GnomAD2 exomes
AF:
0.760
AC:
190300
AN:
250414
AF XY:
0.777
show subpopulations
Gnomad AFR exome
AF:
0.523
Gnomad AMR exome
AF:
0.547
Gnomad ASJ exome
AF:
0.848
Gnomad EAS exome
AF:
0.675
Gnomad FIN exome
AF:
0.733
Gnomad NFE exome
AF:
0.853
Gnomad OTH exome
AF:
0.794
GnomAD4 exome
AF:
0.833
AC:
1216615
AN:
1460420
Hom.:
512543
Cov.:
50
AF XY:
0.835
AC XY:
606429
AN XY:
726538
show subpopulations
African (AFR)
AF:
0.513
AC:
17153
AN:
33422
American (AMR)
AF:
0.561
AC:
25016
AN:
44612
Ashkenazi Jewish (ASJ)
AF:
0.850
AC:
22187
AN:
26110
East Asian (EAS)
AF:
0.666
AC:
26433
AN:
39660
South Asian (SAS)
AF:
0.814
AC:
70129
AN:
86172
European-Finnish (FIN)
AF:
0.738
AC:
39385
AN:
53386
Middle Eastern (MID)
AF:
0.796
AC:
4578
AN:
5752
European-Non Finnish (NFE)
AF:
0.867
AC:
962917
AN:
1110978
Other (OTH)
AF:
0.809
AC:
48817
AN:
60328
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
0
10287
20574
30860
41147
51434
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
21124
42248
63372
84496
105620
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.730
AC:
110951
AN:
151888
Hom.:
42135
Cov.:
31
AF XY:
0.726
AC XY:
53855
AN XY:
74226
show subpopulations
African (AFR)
AF:
0.531
AC:
21982
AN:
41412
American (AMR)
AF:
0.659
AC:
10037
AN:
15238
Ashkenazi Jewish (ASJ)
AF:
0.856
AC:
2967
AN:
3468
East Asian (EAS)
AF:
0.677
AC:
3468
AN:
5124
South Asian (SAS)
AF:
0.804
AC:
3867
AN:
4812
European-Finnish (FIN)
AF:
0.740
AC:
7809
AN:
10556
Middle Eastern (MID)
AF:
0.745
AC:
219
AN:
294
European-Non Finnish (NFE)
AF:
0.858
AC:
58299
AN:
67960
Other (OTH)
AF:
0.732
AC:
1548
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1369
2737
4106
5474
6843
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
828
1656
2484
3312
4140
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.776
Hom.:
38078
Bravo
AF:
0.710
TwinsUK
AF:
0.874
AC:
3241
ALSPAC
AF:
0.862
AC:
3324
ESP6500AA
AF:
0.545
AC:
2403
ESP6500EA
AF:
0.859
AC:
7384
ExAC
AF:
0.765
AC:
92930
Asia WGS
AF:
0.714
AC:
2485
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Benign
0.041
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.63
FATHMM_MKL
Benign
0.039
N
MetaRNN
Benign
0.0000013
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.5
L
PhyloP100
0.28
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.22
Sift
Benign
0.15
T
Sift4G
Benign
0.14
T
Polyphen
0.63
P
Vest4
0.015
MPC
0.017
ClinPred
0.039
T
GERP RS
2.2
Varity_R
0.048
gMVP
0.088
Mutation Taster
=91/9
polymorphism (auto)

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

Other links and lift over

dbSNP: rs13128286; hg19: chr4-69795626; COSMIC: COSV52358702; API