5-35954390-T-C

Variant summary

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

The ENST00000274278.8(UGT3A1):​c.1384A>G​(p.Ile462Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

UGT3A1
ENST00000274278.8 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.08
Variant links:
Genes affected
UGT3A1 (HGNC:26625): (UDP glycosyltransferase family 3 member A1) Enables glucuronosyltransferase activity. Part of UDP-N-acetylglucosamine transferase complex. [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=0.12015879).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
UGT3A1NM_152404.4 linkuse as main transcriptc.1384A>G p.Ile462Val missense_variant 7/7 ENST00000274278.8 NP_689617.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
UGT3A1ENST00000274278.8 linkuse as main transcriptc.1384A>G p.Ile462Val missense_variant 7/71 NM_152404.4 ENSP00000274278 P1Q6NUS8-1
UGT3A1ENST00000515801.5 linkuse as main transcriptc.*3181A>G 3_prime_UTR_variant, NMD_transcript_variant 8/82 ENSP00000427630

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 GeneticsMar 29, 2022The c.1384A>G (p.I462V) alteration is located in exon 7 (coding exon 7) of the UGT3A1 gene. This alteration results from a A to G substitution at nucleotide position 1384, causing the isoleucine (I) at amino acid position 462 to be replaced by a valine (V). 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
0.12
BayesDel_addAF
Benign
-0.26
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
7.4
DANN
Benign
0.67
DEOGEN2
Benign
0.0044
T
Eigen
Benign
-0.93
Eigen_PC
Benign
-0.83
FATHMM_MKL
Benign
0.62
D
LIST_S2
Benign
0.55
T
M_CAP
Benign
0.0037
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.15
N
MutationTaster
Benign
0.67
D
PrimateAI
Benign
0.41
T
PROVEAN
Benign
0.060
N
REVEL
Benign
0.070
Sift
Benign
1.0
T
Sift4G
Benign
0.096
T
Polyphen
0.0060
B
Vest4
0.052
MutPred
0.66
Loss of helix (P = 0.1299);
MVP
0.014
MPC
0.030
ClinPred
0.070
T
GERP RS
2.3
Varity_R
0.061
gMVP
0.059

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-35954492; API