Variant 4-68931165-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_024743.4(UGT2A3):c.1074T>A(p.Asn358Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,460,268 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

UGT2A3
NM_024743.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.51

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.871

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UGT2A3	NM_024743.4 linkuse as main transcript	c.1074T>A	p.Asn358Lys	missense_variant	4/6	ENST00000251566.9
UGT2A3	XM_011532247.3 linkuse as main transcript	c.1092T>A	p.Asn364Lys	missense_variant	4/6
UGT2A3	XM_047416177.1 linkuse as main transcript	c.207T>A	p.Asn69Lys	missense_variant	4/6
UGT2A3	NR_024010.2 linkuse as main transcript	n.1215T>A		non_coding_transcript_exon_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UGT2A3	ENST00000251566.9 linkuse as main transcript	c.1074T>A	p.Asn358Lys	missense_variant	4/6	1	NM_024743.4	P1
UGT2A3	ENST00000503012.1 linkuse as main transcript	c.*250T>A		3_prime_UTR_variant, NMD_transcript_variant	5/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1460268

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726432

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 27, 2023

The c.1074T>A (p.N358K) alteration is located in exon 4 (coding exon 4) of the UGT2A3 gene. This alteration results from a T to A substitution at nucleotide position 1074, causing the asparagine (N) at amino acid position 358 to be replaced by a lysine (K). 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

Pathogenic

0.87

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.39

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.88

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.87

MetaSVM

Uncertain

-0.036

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

0.79

D;D

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-5.9

REVEL

Benign

0.29

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.012

Polyphen

1.0

Vest4

0.67

MutPred

0.88

Gain of methylation at N358 (P = 0.0163);

MVP

0.54

MPC

0.024

ClinPred

1.0

GERP RS

2.0

Varity_R

0.53

gMVP

0.39

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over