Variant chr4-68565639-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001077.4(UGT2B17):c.806G>A(p.Arg269His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000121 in 1,368,704 control chromosomes in the GnomAD database, including 43 homozygotes. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 20)

Exomes 𝑓: 0.00013 ( 43 hom. )

Consequence

UGT2B17
NM_001077.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.225

Variant links:

Genes affected

UGT2B17 (HGNC:12547): (UDP glucuronosyltransferase family 2 member B17) This gene encodes a member of the uridine diphosphoglucuronosyltransferase protein family. The encoded enzyme catalyzes the transfer of glucuronic acid from uridine diphosphoglucuronic acid to a diverse array of substrates including steroid hormones and lipid-soluble drugs. This process, known as glucuronidation, is an intermediate step in the metabolism of steroids. Copy number variation in this gene is associated with susceptibility to osteoporosis.[provided by RefSeq, Apr 2010]

UGT2B17 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UGT2B17	NM_001077.4 link	c.806G>A	p.Arg269His	missense_variant	Exon 3 of 7	ENST00000317746.3	NP_001068.1	O75795

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UGT2B17	ENST00000317746.3 link	c.806G>A	p.Arg269His	missense_variant	Exon 3 of 7	1	NM_001077.4	ENSP00000320401.2		O75795
UGT2B17	ENST00000684088.1 link	c.56G>A	p.Arg19His	missense_variant	Exon 2 of 5			ENSP00000507374.1		A0A804HJ67

Frequencies

GnomAD3 genomes

AF:

0.0000161

AC:

AN:

123890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000274

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000169

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000509

AC:

AN:

196552

Hom.:

AF XY:

0.0000378

AC XY:

AN XY:

105710

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000303

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000132

AC:

164

AN:

1244814

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

615016

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000536

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000153

Gnomad4 OTH exome

AF:

0.0000789

GnomAD4 genome

AF:

0.0000161

AC:

AN:

123890

Hom.:

Cov.:

AF XY:

0.0000170

AC XY:

AN XY:

58992

show subpopulations

Gnomad4 AFR

AF:

0.0000274

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000169

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000197

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 14, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.806G>A (p.R269H) alteration is located in exon 2 (coding exon 2) of the UGT2B17 gene. This alteration results from a G to A substitution at nucleotide position 806, causing the arginine (R) at amino acid position 269 to be replaced by a histidine (H). 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

0.18

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.58

CADD

Benign

2.3

DANN

Benign

0.82

DEOGEN2

Benign

0.11

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.74

M_CAP

Benign

0.0038

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.92

REVEL

Benign

0.22

Sift

Benign

0.51

Sift4G

Benign

0.24

Vest4

0.14

MutPred

0.81

Loss of sheet (P = 0.1907);

MVP

0.13

MPC

1.1

ClinPred

0.078

GERP RS

0.092

Varity_R

0.029

gMVP

0.55

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over