Genetic Variant NM_001077.4:c.773T>C (chr4-68565672-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 4P and 4B. PP3_StrongBS2

The NM_001077.4(UGT2B17):c.773T>C(p.Leu258Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000229 in 1,367,114 control chromosomes in the GnomAD database, including 76 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 1 hom., cov: 20)

Exomes 𝑓: 0.00025 ( 75 hom. )

Consequence

UGT2B17
NM_001077.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 8.26

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.959

BS2

High Homozygotes in GnomAdExome4 at 75 AR gene

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.773T>C	p.Leu258Pro	missense	Exon 3 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.773T>C	p.Leu258Pro	missense	Exon 3 of 7	ENSP00000320401.2	O75795
UGT2B17	ENST00000893234.1		c.773T>C	p.Leu258Pro	missense	Exon 2 of 6	ENSP00000563293.1
UGT2B17	ENST00000950879.1		c.773T>C	p.Leu258Pro	missense	Exon 2 of 5	ENSP00000620938.1

Frequencies

GnomAD3 genomes

AF:

0.0000482

AC:

AN:

124402

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000101

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000717

AC:

AN:

195210

AF XY:

0.0000857

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:

0.000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000247

AC:

307

AN:

1242712

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

153

AN XY:

613844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30524

American (AMR)

AF:

0.00

AC:

AN:

36988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22586

East Asian (EAS)

AF:

0.00

AC:

AN:

10458

South Asian (SAS)

AF:

0.00

AC:

AN:

55572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4870

European-Non Finnish (NFE)

AF:

0.000286

AC:

283

AN:

989436

Other (OTH)

AF:

0.000474

AC:

AN:

50620

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.0000482

AC:

AN:

124402

Hom.:

Cov.:

AF XY:

0.0000506

AC XY:

AN XY:

59230

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

36634

American (AMR)

AF:

0.00

AC:

AN:

11910

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2982

East Asian (EAS)

AF:

0.00

AC:

AN:

1310

South Asian (SAS)

AF:

0.00

AC:

AN:

2702

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

274

European-Non Finnish (NFE)

AF:

0.000101

AC:

AN:

59204

Other (OTH)

AF:

0.00

AC:

AN:

1680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000843

Hom.:

ExAC

AF:

0.0000692

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Pathogenic

0.36

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Uncertain

0.33

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.80

M_CAP

Benign

0.0098

MetaRNN

Pathogenic

0.96

MetaSVM

Uncertain

0.15

MutationAssessor

Pathogenic

4.6

PhyloP100

8.3

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-6.3

REVEL

Pathogenic

0.71

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.85

MVP

0.70

MPC

2.5

ClinPred

1.0

GERP RS

2.5

Varity_R

0.95

gMVP

0.88

Mutation Taster

=63/37

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