Variant chr4-69204469-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_001073.3(UGT2B11):c.1271A>G(p.Asp424Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UGT2B11
NM_001073.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

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:

(HGNC:):

links:

Genome browser will be placed here

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	UniProt
UGT2B11	NM_001073.3 linkuse as main transcript	c.1271A>G	p.Asp424Gly	missense_variant	5/6	ENST00000446444.2	NP_001064.1
LOC105377267	NR_136191.1 linkuse as main transcript	n.597+3185T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
UGT2B11	ENST00000446444.2 linkuse as main transcript	c.1271A>G	p.Asp424Gly	missense_variant	5/6	1	NM_001073.3	ENSP00000387683	P1
	ENST00000504301.5 linkuse as main transcript	n.484+3891T>C		intron_variant, non_coding_transcript_variant		5
UGT2B11	ENST00000513315.1 linkuse as main transcript	n.395A>G		non_coding_transcript_exon_variant	2/2	3
	ENST00000505646.1 linkuse as main transcript	n.272+3185T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.85e-7

AC:

AN:

1460226

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726442

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:

9.00e-7

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

Oct 27, 2023

The c.1271A>G (p.D424G) alteration is located in exon 5 (coding exon 5) of the UGT2B11 gene. This alteration results from a A to G substitution at nucleotide position 1271, causing the aspartic acid (D) at amino acid position 424 to be replaced by a glycine (G). 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

0.26

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.093

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.67

MetaSVM

Benign

-0.58

MutationAssessor

Pathogenic

3.1

MutationTaster

Benign

1.0

PrimateAI

Benign

0.42

PROVEAN

Pathogenic

-6.4

REVEL

Benign

0.12

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.036

Polyphen

0.94

Vest4

0.34

MutPred

0.61

Loss of stability (P = 0.0291);

MVP

0.73

MPC

0.047

ClinPred

0.93

GERP RS

0.49

Varity_R

0.37

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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