rs800667

Positions:

• chr7-99849618-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000354829.7(CYP3A43):​c.594T>C​(p.Asn198=) 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 ENST00000354829.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.623

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.594T>C	p.Asn198=	synonymous_variant	7/13	ENST00000354829.7	NP_476436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7	c.594T>C	p.Asn198=	synonymous_variant	7/13	1	NM_057095.3	ENSP00000346887	A1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29534 AN: 152040 Hom.: 5801 Cov.: 32

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

GnomAD3 exomes AF: 0.0963 AC: 24101 AN: 250172 Hom.: 2899 AF XY: 0.0886 AC XY: 11976 AN XY: 135160

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 SAS exome AF: 0.0677

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.: 31 AF XY: 0.0767 AC XY: 55693 AN XY: 726412

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.0931

Gnomad4 ASJ exome AF: 0.0908

Gnomad4 EAS exome AF: 0.000428

Gnomad4 SAS exome AF: 0.0735

Gnomad4 FIN exome AF: 0.0604

Gnomad4 NFE exome AF: 0.0661

Gnomad4 OTH exome AF: 0.0939

GnomAD4 genome AF: 0.195 AC: 29605 AN: 152160 Hom.: 5822 Cov.: 32 AF XY: 0.189 AC XY: 14091 AN XY: 74414

Gnomad4 AFR AF: 0.510

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0740

Gnomad4 FIN AF: 0.0582

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.169

Alfa AF: 0.0947 Hom.: 3184

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
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	4.4
DANN	Benign	0.33
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.15	T
MetaRNN	Benign	0.000044	T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
REVEL	Benign	0.20
Sift4G	Pathogenic	0.0	D
Vest4		0.041
ClinPred		0.00051	T
GERP RS		-3.1

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

LitVar

Other links and lift over

dbSNP: rs800667; hg19: chr7-99447241;