4-69212614-C-A

Variant names:

• chr4-69212614-C-A
• rs780564592
• NM_001073.3:c.829G>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001073.3(UGT2B11):​c.829G>T​(p.Val277Phe) 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 pathogenic 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. V277I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UGT2B11 NM_001073.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 1 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.848

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.829G>T	p.Val277Phe	missense	Exon 2 of 6	NP_001064.1	O75310
	LOC105377267	NR_136191.1		n.679+1467C>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.829G>T	p.Val277Phe	missense	Exon 2 of 6	ENSP00000387683.1	O75310
	ENSG00000250696	ENST00000504301.5	TSL:5	n.566+1467C>A		intron	N/A
	ENSG00000250696	ENST00000505646.1	TSL:2	n.354+1467C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.099	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.061
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.70	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.016	T
MetaRNN	Pathogenic	0.85	D
MetaSVM	Uncertain	-0.25	T
MutationAssessor	Pathogenic	3.9	H
PhyloP100		-0.27
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-4.0	D
REVEL	Uncertain	0.44
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.99	D
Vest4		0.77
MutPred		0.67		Loss of stability (P = 0.126)
MVP		0.54
MPC		0.053
ClinPred		1.0	D
GERP RS		1.1
Varity_R		0.74
gMVP		0.54
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780564592; hg19: chr4-70078332;