rs61469810

Positions:

• chr7-99836454-TA-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP5 BA1

The NM_057095.3(CYP3A43):​c.74del​(p.Tyr25LeufsTer65) variant causes a frameshift, splice region change. The variant allele was found at a frequency of 0.047 in 1,612,084 control chromosomes in the GnomAD database, including 3,864 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in Lovd as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.099 (1491 hom., cov: 31)
  • Exomes 𝑓: 0.042 (2373 hom.)
• Consequence: CYP3A43 NM_057095.3 frameshift, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33

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 -7 ACMG points.

• PP5: Variant 7-99836454-TA-T is Pathogenic according to our data. Variant chr7-99836454-TA-T is described in Lovd as [Pathogenic].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP3A43	NM_057095.3	c.74del	p.Tyr25LeufsTer65	frameshift_variant, splice_region_variant	2/13	ENST00000354829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP3A43	ENST00000354829.7	c.74del	p.Tyr25LeufsTer65	frameshift_variant, splice_region_variant	2/13	1	NM_057095.3	A1

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 14969 AN: 152126 Hom.: 1488 Cov.: 31

Gnomad AFR AF: 0.255

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0569

Gnomad ASJ AF: 0.0527

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0592

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.0377

Gnomad OTH AF: 0.0985

GnomAD3 exomes AF: 0.0505 AC: 12637 AN: 250348 Hom.: 798 AF XY: 0.0483 AC XY: 6533 AN XY: 135286

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.0353

Gnomad ASJ exome AF: 0.0573

Gnomad EAS exome AF: 0.000273

Gnomad SAS exome AF: 0.0526

Gnomad FIN exome AF: 0.0201

Gnomad NFE exome AF: 0.0376

Gnomad OTH exome AF: 0.0454

GnomAD4 exome AF: 0.0416 AC: 60746 AN: 1459840 Hom.: 2373 Cov.: 29 AF XY: 0.0419 AC XY: 30425 AN XY: 726224

Gnomad4 AFR exome AF: 0.271

Gnomad4 AMR exome AF: 0.0385

Gnomad4 ASJ exome AF: 0.0572

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0573

Gnomad4 FIN exome AF: 0.0194

Gnomad4 NFE exome AF: 0.0351

Gnomad4 OTH exome AF: 0.0517

GnomAD4 genome AF: 0.0985 AC: 15000 AN: 152244 Hom.: 1491 Cov.: 31 AF XY: 0.0970 AC XY: 7222 AN XY: 74454

Gnomad4 AFR AF: 0.255

Gnomad4 AMR AF: 0.0568

Gnomad4 ASJ AF: 0.0527

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0593

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0377

Gnomad4 OTH AF: 0.0974

Alfa AF: 0.0302 Hom.: 33

Bravo AF: 0.107

Asia WGS AF: 0.0350 AC: 121 AN: 3478

EpiCase AF: 0.0426

EpiControl AF: 0.0426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs61469810; hg19: chr7-99434077; COSMIC: COSV55937274;