Variant chr4-69485260-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021139.3(UGT2B4):c.1258A>G(p.Met420Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

UGT2B4
NM_021139.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.00

Variant links:

Genes affected

UGT2B4 (HGNC:12553): (UDP glucuronosyltransferase family 2 member B4) Enables glucuronosyltransferase activity. Involved in cellular glucuronidation and estrogen metabolic process. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

UGT2B4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UGT2B4	NM_021139.3 linkuse as main transcript	c.1258A>G	p.Met420Val	missense_variant	5/6	ENST00000305107.7	NP_066962.2
UGT2B4	NM_001297616.2 linkuse as main transcript	c.850A>G	p.Met284Val	missense_variant	6/7		NP_001284545.1
UGT2B4	NM_001297615.2 linkuse as main transcript	c.1090+1349A>G		intron_variant			NP_001284544.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B4	ENST00000305107.7 linkuse as main transcript	c.1258A>G	p.Met420Val	missense_variant	5/6	1	NM_021139.3	ENSP00000305221	P1	P06133-1
UGT2B4	ENST00000512583.5 linkuse as main transcript	c.1090+1349A>G		intron_variant		1		ENSP00000421290		P06133-3
UGT2B4	ENST00000502655.5 linkuse as main transcript	n.1135A>G		non_coding_transcript_exon_variant	6/6	5
UGT2B4	ENST00000506580.5 linkuse as main transcript	n.872+1349A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251440

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

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 submitter

clinical testing

Ambry Genetics

May 16, 2024

The c.1258A>G (p.M420V) alteration is located in exon 5 (coding exon 5) of the UGT2B4 gene. This alteration results from a A to G substitution at nucleotide position 1258, causing the methionine (M) at amino acid position 420 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

0.11

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.33

CADD

Benign

9.8

DANN

Benign

0.72

DEOGEN2

Benign

0.27

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.80

M_CAP

Benign

0.0068

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.4

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.15

Sift

Benign

0.030

Sift4G

Benign

0.11

Polyphen

0.084

Vest4

0.35

MutPred

0.78

Loss of catalytic residue at M420 (P = 0.1793);

MVP

0.20

MPC

0.015

ClinPred

0.25

GERP RS

2.0

Varity_R

0.39

gMVP

0.20

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