chr4-69200654-C-A

Variant names:

• chr4-69200654-C-A
• rs754330334
• NM_001073.3:c.1376G>T

Variant summary

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

The NM_001073.3(UGT2B11):​c.1376G>T​(p.Arg459Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,396 control chromosomes in the GnomAD database, with no homozygous occurrence. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R459Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.204
• Publications: 0 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B11	NM_001073.3	MANE Select	c.1376G>T	p.Arg459Leu	missense	Exon 6 of 6	NP_001064.1	O75310
	LOC105377267	NR_136191.1		n.484+76C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UGT2B11	ENST00000446444.2	TSL:1 MANE Select	c.1376G>T	p.Arg459Leu	missense	Exon 6 of 6	ENSP00000387683.1	O75310
	ENSG00000250696	ENST00000766440.1		n.427C>A		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000250696	ENST00000504301.5	TSL:5	n.484+76C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460396 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726538

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26078

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111016

Other (OTH) AF: 0.00 AC: 0 AN: 60292

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.061	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.20
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.1	D
REVEL	Benign	0.12
Sift	Benign	0.10	T
Sift4G	Benign	0.47	T
Polyphen		0.043	B
Vest4		0.16
MutPred		0.71		Loss of disorder (P = 0.085)
MVP		0.56
MPC		0.064
ClinPred		0.80	D
GERP RS		1.3
Varity_R		0.22
gMVP		0.25
Mutation Taster		=97/3	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: rs754330334; hg19: chr4-70066372;