Variant 4-68929859-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_024743.4(UGT2A3):c.1538C>T(p.Ser513Phe) 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Failed GnomAD Quality Control

Consequence

UGT2A3
NM_024743.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0480

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]

UGT2A3 links:

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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=0.07770857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UGT2A3	NM_024743.4 linkuse as main transcript	c.1538C>T	p.Ser513Phe	missense_variant	6/6	ENST00000251566.9	NP_079019.3
UGT2A3	XM_011532247.3 linkuse as main transcript	c.1556C>T	p.Ser519Phe	missense_variant	6/6		XP_011530549.1
UGT2A3	XM_047416177.1 linkuse as main transcript	c.671C>T	p.Ser224Phe	missense_variant	6/6		XP_047272133.1
UGT2A3	NR_024010.2 linkuse as main transcript	n.1679C>T		non_coding_transcript_exon_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2A3	ENST00000251566.9 linkuse as main transcript	c.1538C>T	p.Ser513Phe	missense_variant	6/6	1	NM_024743.4	ENSP00000251566	P1
UGT2A3	ENST00000503012.1 linkuse as main transcript	c.*714C>T		3_prime_UTR_variant, NMD_transcript_variant	7/7	2		ENSP00000424092

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151934

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000658

AC:

AN:

151934

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

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 submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.1538C>T (p.S513F) alteration is located in exon 6 (coding exon 6) of the UGT2A3 gene. This alteration results from a C to T substitution at nucleotide position 1538, causing the serine (S) at amino acid position 513 to be replaced by a phenylalanine (F). 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

0.084

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.72

DANN

Benign

0.086

DEOGEN2

Benign

0.027

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

M_CAP

Benign

0.0085

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.99

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.3

REVEL

Benign

0.061

Sift

Benign

0.32

Sift4G

Benign

0.33

Polyphen

0.020

Vest4

0.10

MutPred

0.58

Loss of catalytic residue at S513 (P = 0.0152);

MVP

0.076

MPC

0.0055

ClinPred

0.26

GERP RS

-3.6

Varity_R

0.048

gMVP

0.15

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over