4-69205525-G-T

Position:

• chr4-69205525-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001073.3(UGT2B11):​c.1045C>A​(p.Leu349Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.03

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]

(HGNC:):

ACMG classification

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=0.15727183).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B11	NM_001073.3	c.1045C>A	p.Leu349Ile	missense_variant	4/6	ENST00000446444.2	NP_001064.1
LOC105377267	NR_136191.1	n.597+4241G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B11	ENST00000446444.2	c.1045C>A	p.Leu349Ile	missense_variant	4/6	1	NM_001073.3	ENSP00000387683	P1
	ENST00000504301.5	n.484+4947G>T		intron_variant, non_coding_transcript_variant		5
UGT2B11	ENST00000513315.1	n.169C>A		non_coding_transcript_exon_variant	1/2	3
	ENST00000505646.1	n.272+4241G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2023

The c.1045C>A (p.L349I) 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 1045, causing the leucine (L) at amino acid position 349 to be replaced by an isoleucine (I). 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	0.099
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.44
DANN	Benign	0.45
DEOGEN2	Benign	0.0030	T
Eigen	Benign	-2.2
Eigen_PC	Benign	-2.3
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.11	N
REVEL	Benign	0.084
Sift	Uncertain	0.019	D
Sift4G	Benign	0.12	T
Polyphen		0.0	B
Vest4		0.23
MutPred		0.37		Loss of catalytic residue at L349 (P = 0.0198);
MVP		0.20
MPC		0.010
ClinPred		0.18	T
GERP RS		-4.0
Varity_R		0.10
gMVP		0.078

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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.

Other links and lift over

hg19: chr4-70071243;