4-68929997-C-T

Variant summary

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

The ENST00000251566.9(UGT2A3):​c.1400G>A​(p.Arg467His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,613,378 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R467C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )

Consequence

UGT2A3
ENST00000251566.9 missense

Scores

1
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.84
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 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=0.228941).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UGT2A3NM_024743.4 linkuse as main transcriptc.1400G>A p.Arg467His missense_variant 6/6 ENST00000251566.9 NP_079019.3
UGT2A3XM_011532247.3 linkuse as main transcriptc.1418G>A p.Arg473His missense_variant 6/6 XP_011530549.1
UGT2A3XM_047416177.1 linkuse as main transcriptc.533G>A p.Arg178His missense_variant 6/6 XP_047272133.1
UGT2A3NR_024010.2 linkuse as main transcriptn.1541G>A non_coding_transcript_exon_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UGT2A3ENST00000251566.9 linkuse as main transcriptc.1400G>A p.Arg467His missense_variant 6/61 NM_024743.4 ENSP00000251566 P1
UGT2A3ENST00000503012.1 linkuse as main transcriptc.*576G>A 3_prime_UTR_variant, NMD_transcript_variant 7/72 ENSP00000424092

Frequencies

GnomAD3 genomes
AF:
0.0000461
AC:
7
AN:
151934
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000398
AC:
10
AN:
250978
Hom.:
0
AF XY:
0.0000590
AC XY:
8
AN XY:
135634
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.000163
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000643
AC:
94
AN:
1461444
Hom.:
0
Cov.:
36
AF XY:
0.0000674
AC XY:
49
AN XY:
727042
show subpopulations
Gnomad4 AFR exome
AF:
0.0000598
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000711
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000461
AC:
7
AN:
151934
Hom.:
0
Cov.:
32
AF XY:
0.0000539
AC XY:
4
AN XY:
74182
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000986
Hom.:
0
Bravo
AF:
0.0000378
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.0000546
EpiControl
AF:
0.0000593

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 GeneticsJul 20, 2022The c.1400G>A (p.R467H) alteration is located in exon 6 (coding exon 6) of the UGT2A3 gene. This alteration results from a G to A substitution at nucleotide position 1400, causing the arginine (R) at amino acid position 467 to be replaced by a histidine (H). 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
0.20
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
19
DANN
Benign
0.95
DEOGEN2
Benign
0.23
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.57
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-0.57
T
MutationAssessor
Pathogenic
3.1
M
MutationTaster
Benign
0.54
D;D
PrimateAI
Benign
0.40
T
PROVEAN
Uncertain
-4.3
D
REVEL
Uncertain
0.37
Sift
Benign
0.053
T
Sift4G
Benign
0.067
T
Polyphen
0.19
B
Vest4
0.33
MVP
0.42
MPC
0.0059
ClinPred
0.55
D
GERP RS
1.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.29

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: rs553189244; hg19: chr4-69795715; COSMIC: COSV52359826; API