Variant 4-68567898-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001077.4(UGT2B17):c.587C>G(p.Pro196Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000363 in 1,378,958 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000024 ( 1 hom., cov: 20)

Exomes 𝑓: 0.0000016 ( 0 hom. )

Consequence

UGT2B17
NM_001077.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.80

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.878

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UGT2B17	NM_001077.4 linkuse as main transcript	c.587C>G	p.Pro196Arg	missense_variant	2/7	ENST00000317746.3	NP_001068.1	O75795

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UGT2B17	ENST00000317746.3 linkuse as main transcript	c.587C>G	p.Pro196Arg	missense_variant	2/7	1	NM_001077.4	ENSP00000320401.2		O75795
UGT2B17	ENST00000684088.1 linkuse as main transcript	c.-26-2178C>G		intron_variant				ENSP00000507374.1		A0A804HJ67

Frequencies

GnomAD3 genomes

AF:

0.0000238

AC:

AN:

125814

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000815

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000499

AC:

AN:

200506

Hom.:

AF XY:

0.00000926

AC XY:

AN XY:

107954

show subpopulations

Gnomad AFR exome

AF:

0.0000663

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000160

AC:

AN:

1253144

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

619872

show subpopulations

Gnomad4 AFR exome

AF:

0.0000652

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000238

AC:

AN:

125814

Hom.:

Cov.:

AF XY:

0.0000333

AC XY:

AN XY:

59990

show subpopulations

Gnomad4 AFR

AF:

0.0000815

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:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 06, 2024

The c.587C>G (p.P196R) alteration is located in exon 1 (coding exon 1) of the UGT2B17 gene. This alteration results from a C to G substitution at nucleotide position 587, causing the proline (P) at amino acid position 196 to be replaced by an arginine (R). 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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.0066

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Benign

0.14

Eigen_PC

Benign

-0.085

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0047

MetaRNN

Pathogenic

0.88

MetaSVM

Uncertain

-0.24

MutationAssessor

Pathogenic

4.3

PrimateAI

Uncertain

0.54

PROVEAN

Pathogenic

-8.5

REVEL

Uncertain

0.32

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0070

Vest4

0.72

MVP

0.60

MPC

0.49

ClinPred

1.0

GERP RS

1.8

Varity_R

0.76

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.26

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.26

Position offset: 5

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