Genetic Variant UGT3A1:p.Gly494Ala (chr5-35954293-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152404.4(UGT3A1):c.1481G>C(p.Gly494Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. G494W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

UGT3A1
NM_152404.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.195

Publications

0 publications found

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]

UGT3A1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07411882).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152404.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT3A1	NM_152404.4	MANE Select	c.1481G>C	p.Gly494Ala	missense	Exon 7 of 7	NP_689617.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UGT3A1	ENST00000274278.8	TSL:1 MANE Select	c.1481G>C	p.Gly494Ala	missense	Exon 7 of 7	ENSP00000274278.3	Q6NUS8-1
UGT3A1	ENST00000876682.1		c.1379G>C	p.Gly460Ala	missense	Exon 6 of 6	ENSP00000546741.1
UGT3A1	ENST00000876683.1		c.602G>C	p.Gly201Ala	missense	Exon 4 of 4	ENSP00000546742.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461874

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.8

(source)

DANN

Benign

0.084

DEOGEN2

Benign

0.0015

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.77

M_CAP

Benign

0.0099

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.85

MutationAssessor

Benign

-0.47

PhyloP100

-0.20

PrimateAI

Benign

0.33

PROVEAN

Benign

1.0

REVEL

Benign

0.081

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.019

Vest4

0.10

MutPred

0.64

Loss of catalytic residue at L495 (P = 0.159)

MVP

0.040

MPC

0.050

ClinPred

0.094

GERP RS

-2.8

Varity_R

0.061

gMVP

0.069

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over