rs28383468

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000777.5(CYP3A5):c.88C>T(p.His30Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00786 in 1,613,744 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 8 hom., cov: 31)

Exomes 𝑓: 0.0081 ( 59 hom. )

Consequence

CYP3A5
NM_000777.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.60

Publications

22 publications found

Variant links:

Genes affected

CYP3A5 (HGNC:2638): (cytochrome P450 family 3 subfamily A member 5) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The encoded protein metabolizes drugs as well as the steroid hormones testosterone and progesterone. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Two pseudogenes of this gene have been identified within this cluster on chromosome 7. Expression of this gene is widely variable among populations, and a single nucleotide polymorphism that affects transcript splicing has been associated with susceptibility to hypertensions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

CYP3A5 links:

ZSCAN25 (HGNC:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [provided by RefSeq, Jul 2008]

ZSCAN25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004989326).

BP6

Variant 7-99676192-G-A is Benign according to our data. Variant chr7-99676192-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2657725.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 900 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A5	NM_000777.5 link	c.88C>T	p.His30Tyr	missense_variant	Exon 2 of 13	ENST00000222982.8	NP_000768.1	P20815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A5	ENST00000222982.8 link	c.88C>T	p.His30Tyr	missense_variant	Exon 2 of 13	1	NM_000777.5	ENSP00000222982.4		P20815-1

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

901

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00164

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00641

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00264

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00941

Gnomad OTH

AF:

0.00716

GnomAD2 exomes

AF:

0.00693

AC:

1741

AN:

251308

AF XY:

0.00725

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00474

Gnomad ASJ exome

AF:

0.00735

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00370

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00806

AC:

11786

AN:

1461428

Hom.:

Cov.:

AF XY:

0.00798

AC XY:

5800

AN XY:

727014

show subpopulations

African (AFR)

AF:

0.00122

AC:

AN:

33470

American (AMR)

AF:

0.00470

AC:

210

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00712

AC:

186

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39686

South Asian (SAS)

AF:

0.00596

AC:

514

AN:

86254

European-Finnish (FIN)

AF:

0.00417

AC:

222

AN:

53254

Middle Eastern (MID)

AF:

0.00694

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00911

AC:

10127

AN:

1111780

Other (OTH)

AF:

0.00737

AC:

445

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.443

Heterozygous variant carriers

647

1293

1940

2586

3233

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

380

760

1140

1520

1900

<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:

0.00591

AC:

900

AN:

152316

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.00164

AC:

AN:

41568

American (AMR)

AF:

0.00634

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00539

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00264

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00941

AC:

640

AN:

68026

Other (OTH)

AF:

0.00709

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00266

Hom.:

Bravo

AF:

0.00572

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00136

AC:

ESP6500EA

AF:

0.00953

AC:

ExAC

AF:

0.00746

AC:

906

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.0112

EpiControl

AF:

0.0106

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

CYP3A5: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.0044

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.81

T;T

MetaRNN

Benign

0.0050

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

L;L

PhyloP100

1.6

PROVEAN

Benign

-1.7

N;D

REVEL

Benign

0.071

Sift

Benign

0.55

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0040

B;.

Vest4

0.16

MVP

0.16

MPC

0.25

ClinPred

0.0046

GERP RS

1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.049

gMVP

0.84

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over