Genetic Variant UGT2B17:p.Ala413Asp (chr4-68550752-G-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.1238C>A(p.Ala413Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000036 in 1,386,996 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: 𝑓 0.0000080 ( 0 hom., cov: 20)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

UGT2B17
NM_001077.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

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, 0.982

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.1238C>A	p.Ala413Asp	missense	Exon 6 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.1238C>A	p.Ala413Asp	missense	Exon 6 of 7	ENSP00000320401.2	O75795
UGT2B17	ENST00000893234.1		c.1238C>A	p.Ala413Asp	missense	Exon 5 of 6	ENSP00000563293.1
UGT2B17	ENST00000950879.1		c.1106C>A	p.Ala369Asp	missense	Exon 4 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes

AF:

0.00000798

AC:

AN:

125248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000273

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

GnomAD2 exomes

AF:

0.00000493

AC:

AN:

202882

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000983

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000317

AC:

AN:

1261748

Hom.:

Cov.:

AF XY:

0.00000321

AC XY:

AN XY:

623624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30920

American (AMR)

AF:

0.00

AC:

AN:

38182

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22672

East Asian (EAS)

AF:

0.00

AC:

AN:

10792

South Asian (SAS)

AF:

0.00

AC:

AN:

57562

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4896

European-Non Finnish (NFE)

AF:

0.00000399

AC:

AN:

1003176

Other (OTH)

AF:

0.00

AC:

AN:

51344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.563

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

AF:

0.00000798

AC:

AN:

125248

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

59658

show subpopulations

African (AFR)

AF:

0.0000273

AC:

AN:

36684

American (AMR)

AF:

0.00

AC:

AN:

12108

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2946

East Asian (EAS)

AF:

0.00

AC:

AN:

1320

South Asian (SAS)

AF:

0.00

AC:

AN:

2668

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7530

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59320

Other (OTH)

AF:

0.00

AC:

AN:

1682

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

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

0.96

BayesDel_addAF

Pathogenic

0.34

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.49

Eigen

Benign

0.15

Eigen_PC

Benign

-0.030

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.0034

MetaRNN

Pathogenic

0.98

MetaSVM

Uncertain

-0.054

MutationAssessor

Pathogenic

4.4

PhyloP100

3.2

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-5.8

REVEL

Uncertain

0.51

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Vest4

0.78

MutPred

0.89

Gain of disorder (P = 0.0584)

MVP

0.59

MPC

2.4

ClinPred

1.0

GERP RS

2.8

Varity_R

0.89

gMVP

0.76

Mutation Taster

=85/15

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over