4-69212577-G-A

Variant names:

• chr4-69212577-G-A
• rs3890590
• NM_001073.3:c.866C>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001073.3(UGT2B11):​c.866C>T​(p.Pro289Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000344 in 1,455,440 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.70
• Publications: 3 publications found

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]

ENSG00000250696 (HGNC:58803):

LOC105377267 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B11	NM_001073.3	MANE Select	c.866C>T	p.Pro289Leu	missense	Exon 2 of 6	NP_001064.1
	LOC105377267	NR_136191.1		n.679+1430G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B11	ENST00000446444.2	TSL:1 MANE Select	c.866C>T	p.Pro289Leu	missense	Exon 2 of 6	ENSP00000387683.1
	ENSG00000250696	ENST00000504301.5	TSL:5	n.566+1430G>A		intron	N/A
	ENSG00000250696	ENST00000505646.1	TSL:2	n.354+1430G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000810 AC: 2 AN: 246916 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000110

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1455440 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 723958

African (AFR) AF: 0.00 AC: 0 AN: 32934

American (AMR) AF: 0.00 AC: 0 AN: 44060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25964

East Asian (EAS) AF: 0.0000761 AC: 3 AN: 39404

South Asian (SAS) AF: 0.00 AC: 0 AN: 85280

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108654

Other (OTH) AF: 0.0000333 AC: 2 AN: 60088

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000144 Hom.: 0

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.025
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.8	H
PhyloP100		6.7
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-9.3	D
REVEL	Benign	0.26
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.033	D
Polyphen		0.78	P
Vest4		0.37
MutPred		0.59		Loss of glycosylation at P289 (P = 0.0185)
MVP		0.72
MPC		0.065
ClinPred		1.0	D
GERP RS		2.0
Varity_R		0.71
gMVP		0.42
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs3890590; hg19: chr4-70078295;