7-99848168-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_057095.3(CYP3A43):c.435G>T(p.Met145Ile) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00181 in 1,614,070 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0098 ( 27 hom., cov: 32)

Exomes 𝑓: 0.00097 ( 20 hom. )

Consequence

CYP3A43
NM_057095.3 missense, splice_region

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.80

Publications

11 publications found

Variant links:

Genes affected

CYP3A43 (HGNC:17450): (cytochrome P450 family 3 subfamily A member 43) 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 has a low level of testosterone hydroxylase activity, and may play a role in aging mechanisms and cancer progression. This gene is part of a cluster of cytochrome P450 genes on chromosome 7q21.1. Alternate splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

CYP3A43 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061385036).

BP6

Variant 7-99848168-G-T is Benign according to our data. Variant chr7-99848168-G-T is described in ClinVar as [Benign]. Clinvar id is 735139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00984 (1498/152288) while in subpopulation AFR AF = 0.0348 (1447/41554). AF 95% confidence interval is 0.0333. There are 27 homozygotes in GnomAd4. There are 706 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A43	NM_057095.3 link	c.435G>T	p.Met145Ile	missense_variant, splice_region_variant	Exon 6 of 13	ENST00000354829.7	NP_476436.1	Q9HB55-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7 link	c.435G>T	p.Met145Ile	missense_variant, splice_region_variant	Exon 6 of 13	1	NM_057095.3	ENSP00000346887.3		Q9HB55-1

Frequencies

GnomAD3 genomes

AF:

0.00984

AC:

1497

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0349

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.0100

GnomAD2 exomes

AF:

0.00255

AC:

641

AN:

251256

AF XY:

0.00190

show subpopulations

Gnomad AFR exome

AF:

0.0356

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000972

AC:

1421

AN:

1461782

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

600

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.0361

AC:

1207

AN:

33478

American (AMR)

AF:

0.00168

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.000520

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111948

Other (OTH)

AF:

0.00185

AC:

112

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00984

AC:

1498

AN:

152288

Hom.:

Cov.:

AF XY:

0.00948

AC XY:

706

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0348

AC:

1447

AN:

41554

American (AMR)

AF:

0.00150

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68002

Other (OTH)

AF:

0.00994

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

142

213

284

355

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00338

Hom.:

Bravo

AF:

0.0114

ESP6500AA

AF:

0.0345

AC:

152

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00337

AC:

409

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.70

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

T;.;.

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;D;D

MetaRNN

Benign

0.0061

T;T;T

MetaSVM

Benign

-0.69

MutationAssessor

Pathogenic

3.3

M;M;M

PhyloP100

6.8

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Uncertain

0.32

Sift

Benign

0.045

D;D;D

Sift4G

Benign

0.084

T;D;T

Polyphen

0.88

P;P;.

Vest4

0.65

MutPred

0.65

Gain of catalytic residue at P147 (P = 0.0391);Gain of catalytic residue at P147 (P = 0.0391);Gain of catalytic residue at P147 (P = 0.0391);

MVP

0.66

MPC

0.20

ClinPred

0.11

GERP RS

2.9

Varity_R

0.57

gMVP

0.81

Mutation Taster

=57/43

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

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

7-99848168-G-T

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