dbSNP rs800667: CYP3A43:p.Asn198Asn (chr7-99849618-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_057095.3(CYP3A43):c.594T>C(p.Asn198Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0888 in 1,612,570 control chromosomes in the GnomAD database, including 14,260 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.19 ( 5822 hom., cov: 32)

Exomes 𝑓: 0.078 ( 8438 hom. )

Consequence

CYP3A43
NM_057095.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.623

Publications

16 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.374087E-5).

BP7

Synonymous conserved (PhyloP=-0.623 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A43	NM_057095.3 link	c.594T>C	p.Asn198Asn	synonymous_variant	Exon 7 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.594T>C	p.Asn198Asn	synonymous_variant	Exon 7 of 13	1	NM_057095.3	ENSP00000346887.3		Q9HB55-1

Frequencies

GnomAD3 genomes

AF:

0.194

AC:

29534

AN:

152040

Hom.:

5801

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.124

Gnomad ASJ

AF:

0.0878

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0740

Gnomad FIN

AF:

0.0582

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0702

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.0963

AC:

24101

AN:

250172

AF XY:

0.0886

show subpopulations

Gnomad AFR exome

AF:

0.525

Gnomad AMR exome

AF:

0.0888

Gnomad ASJ exome

AF:

0.0882

Gnomad EAS exome

AF:

0.000763

Gnomad FIN exome

AF:

0.0595

Gnomad NFE exome

AF:

0.0692

Gnomad OTH exome

AF:

0.0837

GnomAD4 exome

AF:

0.0777

AC:

113513

AN:

1460410

Hom.:

8438

Cov.:

AF XY:

0.0767

AC XY:

55693

AN XY:

726412

show subpopulations

African (AFR)

AF:

0.532

AC:

17692

AN:

33268

American (AMR)

AF:

0.0931

AC:

4138

AN:

44470

Ashkenazi Jewish (ASJ)

AF:

0.0908

AC:

2369

AN:

26088

East Asian (EAS)

AF:

0.000428

AC:

AN:

39696

South Asian (SAS)

AF:

0.0735

AC:

6308

AN:

85792

European-Finnish (FIN)

AF:

0.0604

AC:

3225

AN:

53396

Middle Eastern (MID)

AF:

0.115

AC:

660

AN:

5762

European-Non Finnish (NFE)

AF:

0.0661

AC:

73439

AN:

1111592

Other (OTH)

AF:

0.0939

AC:

5665

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4834

9668

14502

19336

24170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2904

5808

8712

11616

14520

<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:

0.195

AC:

29605

AN:

152160

Hom.:

5822

Cov.:

AF XY:

0.189

AC XY:

14091

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.510

AC:

21135

AN:

41440

American (AMR)

AF:

0.124

AC:

1892

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0878

AC:

305

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5190

South Asian (SAS)

AF:

0.0740

AC:

357

AN:

4822

European-Finnish (FIN)

AF:

0.0582

AC:

617

AN:

10606

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0702

AC:

4777

AN:

68012

Other (OTH)

AF:

0.169

AC:

358

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

912

1823

2735

3646

4558

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.115

Hom.:

7085

Bravo

AF:

0.213

TwinsUK

AF:

0.0696

AC:

258

ALSPAC

AF:

0.0672

AC:

259

ESP6500AA

AF:

0.506

AC:

2230

ESP6500EA

AF:

0.0690

AC:

593

ExAC

AF:

0.105

AC:

12737

Asia WGS

AF:

0.0600

AC:

211

AN:

3478

EpiCase

AF:

0.0704

EpiControl

AF:

0.0725

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.4

(source)

DANN

Benign

0.33

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.15

MetaRNN

Benign

0.000044

MetaSVM

Benign

-0.94

PhyloP100

-0.62

REVEL

Benign

0.20

Sift4G

Pathogenic

0.0

Vest4

0.041

ClinPred

0.00051

GERP RS

-3.1

Mutation Taster

=97/3

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over