Genetic Variant UGT2B11:p.Arg477Gln (chr4-69200600-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_001073.3(UGT2B11):c.1430G>A(p.Arg477Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000453 in 1,612,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

UGT2B11
NM_001073.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

Publications

1 publications found

Variant links:

Genes affected

UGT2B11 (HGNC:12545): (UDP glucuronosyltransferase family 2 member B11) Enables glucuronosyltransferase activity. Involved in estrogen metabolic process and xenobiotic glucuronidation. 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]

UGT2B11 links:

ENSG00000250696 (HGNC:58803):

ENSG00000250696 links:

LOC105377267 (HGNC:):

LOC105377267 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.825

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001073.3. 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
	UGT2B11	NM_001073.3	MANE Select	c.1430G>A	p.Arg477Gln	missense	Exon 6 of 6	NP_001064.1	O75310
	LOC105377267	NR_136191.1		n.484+22C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UGT2B11	ENST00000446444.2	TSL:1 MANE Select	c.1430G>A	p.Arg477Gln	missense	Exon 6 of 6	ENSP00000387683.1	O75310
ENSG00000250696	ENST00000766440.1		n.373C>T		non_coding_transcript_exon	Exon 2 of 2
ENSG00000250696	ENST00000504301.5	TSL:5	n.484+22C>T		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000472

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000319

AC:

AN:

250806

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00000882

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000438

AC:

AN:

1460532

Hom.:

Cov.:

AF XY:

0.0000468

AC XY:

AN XY:

726598

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33380

American (AMR)

AF:

0.00

AC:

AN:

44636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26088

East Asian (EAS)

AF:

0.00

AC:

AN:

39634

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.000524

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

1111116

Other (OTH)

AF:

0.000116

AC:

AN:

60306

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

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

AF:

0.0000593

AC:

AN:

151874

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41486

American (AMR)

AF:

0.00

AC:

AN:

15224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000196

AC:

AN:

5104

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000472

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000442

AC:

AN:

67862

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.547

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000818

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

0.19

BayesDel_addAF

Benign

-0.037

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

Eigen

Benign

-0.062

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.19

LIST_S2

Uncertain

0.95

M_CAP

Benign

0.0098

MetaRNN

Pathogenic

0.83

MetaSVM

Benign

-0.40

MutationAssessor

Pathogenic

3.4

PhyloP100

3.3

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.27

Sift

Uncertain

0.023

Sift4G

Uncertain

0.023

Polyphen

1.0

Vest4

0.17

MutPred

0.87

Loss of methylation at R477 (P = 0.0202)

MVP

0.53

MPC

0.065

ClinPred

0.99

GERP RS

1.3

Varity_R

0.35

gMVP

0.15

Mutation Taster

=88/12

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over