Genetic Variant UGT2B17:p.Asp493Glu (chr4-68537739-A-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001077.4(UGT2B17):c.1479T>A(p.Asp493Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000798 in 1,253,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 20)

Exomes 𝑓: 8.0e-7 ( 0 hom. )

Consequence

UGT2B17
NM_001077.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.367

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.976

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001077.4. 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
	UGT2B17	NM_001077.4	MANE Select	c.1479T>A	p.Asp493Glu	missense	Exon 7 of 7	NP_001068.1	O75795

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UGT2B17	ENST00000317746.3	TSL:1 MANE Select	c.1479T>A	p.Asp493Glu	missense	Exon 7 of 7	ENSP00000320401.2	O75795
UGT2B17	ENST00000893234.1		c.1479T>A	p.Asp493Glu	missense	Exon 6 of 6	ENSP00000563293.1
UGT2B17	ENST00000950879.1		c.1347T>A	p.Asp449Glu	missense	Exon 5 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.98e-7

AC:

AN:

1253250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

619348

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30956

American (AMR)

AF:

0.00

AC:

AN:

38294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22656

East Asian (EAS)

AF:

0.00

AC:

AN:

10790

South Asian (SAS)

AF:

0.00

AC:

AN:

57302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4898

European-Non Finnish (NFE)

AF:

0.00000100

AC:

AN:

995336

Other (OTH)

AF:

0.00

AC:

AN:

51064

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

Eigen

Benign

0.067

Eigen_PC

Benign

-0.059

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.84

M_CAP

Benign

0.0063

MetaRNN

Pathogenic

0.98

MetaSVM

Benign

-0.37

MutationAssessor

Pathogenic

4.3

PhyloP100

0.37

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.72

MutPred

0.92

Gain of helix (P = 0.2294)

MVP

0.45

MPC

1.9

ClinPred

1.0

GERP RS

1.6

Varity_R

0.68

gMVP

0.61

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over