Variant chr7-99652613-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000777.5(CYP3A5):c.1193C>A(p.Thr398Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 1,614,026 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 21 hom. )

Consequence

CYP3A5
NM_000777.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.04

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0249556).

BS2

High AC in GnomAd4 at 461 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP3A5	NM_000777.5 link	c.1193C>A	p.Thr398Asn	missense_variant	11/13	ENST00000222982.8	NP_000768.1	P20815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A5	ENST00000222982.8 link	c.1193C>A	p.Thr398Asn	missense_variant	11/13	1	NM_000777.5	ENSP00000222982.4		P20815-1

Frequencies

GnomAD3 genomes

AF:

0.00303

AC:

461

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000983

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00543

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00325

AC:

817

AN:

251382

Hom.:

AF XY:

0.00314

AC XY:

426

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00124

Gnomad ASJ exome

AF:

0.000496

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00157

Gnomad NFE exome

AF:

0.00623

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00465

AC:

6798

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00456

AC XY:

3313

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.000306

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00174

Gnomad4 NFE exome

AF:

0.00581

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00303

AC:

461

AN:

152234

Hom.:

Cov.:

AF XY:

0.00274

AC XY:

204

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00543

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00501

Hom.:

Bravo

AF:

0.00300

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00488

AC:

ExAC

AF:

0.00352

AC:

428

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00496

EpiControl

AF:

0.00492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.44

CADD

Benign

0.013

DANN

Benign

0.80

DEOGEN2

Benign

0.16

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.82

M_CAP

Benign

0.0090

MetaRNN

Benign

0.025

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.4

PROVEAN

Benign

-1.8

REVEL

Benign

0.11

Sift

Benign

0.046

Sift4G

Uncertain

0.040

Polyphen

0.0030

Vest4

0.21

MVP

0.45

MPC

0.26

ClinPred

0.013

GERP RS

-2.7

Varity_R

0.18

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over