Genetic Variant UGT2B11:p.Ala346Asp (chr4-69205533-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001073.3(UGT2B11):c.1037C>A(p.Ala346Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000048 in 1,458,726 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

UGT2B11
NM_001073.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.927

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:):

ENSG00000250696 links:

Genome browser will be placed here

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=0.20886093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B11	NM_001073.3 link	c.1037C>A	p.Ala346Asp	missense_variant	Exon 4 of 6	ENST00000446444.2	NP_001064.1	O75310

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UGT2B11	ENST00000446444.2 link	c.1037C>A	p.Ala346Asp	missense_variant	Exon 4 of 6	1	NM_001073.3	ENSP00000387683.1	O75310
UGT2B11	ENST00000513315.1 link	n.161C>A		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000250696	ENST00000504301.5 link	n.484+4955G>T		intron_variant	Intron 3 of 4	5
ENSG00000250696	ENST00000505646.1 link	n.272+4249G>T		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250514

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135430

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458726

Hom.:

Cov.:

AF XY:

0.00000689

AC XY:

AN XY:

725784

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1037C>A (p.A346D) alteration is located in exon 4 (coding exon 4) of the UGT2B11 gene. This alteration results from a C to A substitution at nucleotide position 1037, causing the alanine (A) at amino acid position 346 to be replaced by an aspartic acid (D). 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

0.17

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0062

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.033

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.016

MetaRNN

Benign

0.21

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.86

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.96

REVEL

Benign

0.13

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.15

Vest4

0.33

MutPred

0.48

Gain of disorder (P = 0.033);

MVP

0.35

MPC

0.018

ClinPred

0.10

GERP RS

-0.15

Varity_R

0.45

gMVP

0.19

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