7-99859982-C-G

Variant names:

• chr7-99859982-C-G
• rs680055
• NM_057095.3:c.1018C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_057095.3(CYP3A43):​c.1018C>G​(p.Pro340Ala) variant causes a missense change. The variant allele was found at a frequency of 0.066 in 1,601,740 control chromosomes in the GnomAD database, including 6,316 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (2261 hom., cov: 32)
  • Exomes 𝑓: 0.060 (4055 hom.)
• Consequence: CYP3A43 NM_057095.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.25
• Publications: 43 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.004045546).
• BP6: Variant 7-99859982-C-G is Benign according to our data. Variant chr7-99859982-C-G is described in ClinVar as Benign. ClinVar VariationId is 1278238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.1018C>G	p.Pro340Ala	missense_variant	Exon 10 of 13	ENST00000354829.7	NP_476436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7	c.1018C>G	p.Pro340Ala	missense_variant	Exon 10 of 13	1	NM_057095.3	ENSP00000346887.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19075 AN: 151942 Hom.: 2250 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0453

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.111

GnomAD2 exomes AF: 0.0648 AC: 15395 AN: 237488 AF XY: 0.0609

Gnomad AFR exome AF: 0.320

Gnomad AMR exome AF: 0.0407

Gnomad ASJ exome AF: 0.0599

Gnomad EAS exome AF: 0.000495

Gnomad FIN exome AF: 0.0542

Gnomad NFE exome AF: 0.0537

Gnomad OTH exome AF: 0.0604

GnomAD4 exome AF: 0.0597 AC: 86596 AN: 1449680 Hom.: 4055 Cov.: 31 AF XY: 0.0588 AC XY: 42361 AN XY: 720382

African (AFR) AF: 0.321 AC: 10652 AN: 33188

American (AMR) AF: 0.0439 AC: 1907 AN: 43420

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 1453 AN: 25166

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39566

South Asian (SAS) AF: 0.0433 AC: 3623 AN: 83588

European-Finnish (FIN) AF: 0.0522 AC: 2758 AN: 52828

Middle Eastern (MID) AF: 0.0928 AC: 529 AN: 5698

European-Non Finnish (NFE) AF: 0.0557 AC: 61669 AN: 1106320

Other (OTH) AF: 0.0667 AC: 3996 AN: 59906

GnomAD4 genome AF: 0.126 AC: 19124 AN: 152060 Hom.: 2261 Cov.: 32 AF XY: 0.123 AC XY: 9149 AN XY: 74356

African (AFR) AF: 0.312 AC: 12929 AN: 41414

American (AMR) AF: 0.0750 AC: 1147 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5180

South Asian (SAS) AF: 0.0449 AC: 216 AN: 4810

European-Finnish (FIN) AF: 0.0552 AC: 585 AN: 10590

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0552 AC: 3756 AN: 67994

Other (OTH) AF: 0.110 AC: 232 AN: 2108

Alfa AF: 0.0649 Hom.: 345

Bravo AF: 0.134

TwinsUK AF: 0.0631 AC: 234

ALSPAC AF: 0.0597 AC: 230

ESP6500AA AF: 0.304 AC: 1338

ESP6500EA AF: 0.0488 AC: 420

ExAC AF: 0.0668 AC: 8108

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Oct 28, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 25150845) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Benign	0.83
DEOGEN2	Benign	0.12	T;.;.;.;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.97	D;D;D;D;D;D
MetaRNN	Benign	0.0040	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;.;.;M;M
PhyloP100		4.3
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-7.2	D;D;D;D;D;D
REVEL	Benign	0.15
Sift	Uncertain	0.021	D;D;T;D;D;D
Sift4G	Benign	0.17	T;T;T;T;D;T
Polyphen		0.015	B;.;.;.;P;.
Vest4		0.16
MPC		0.025
ClinPred		0.083	T
GERP RS		1.6
Varity_R		0.66
gMVP		0.52
Mutation Taster		=92/8	polymorphism (auto)

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

Other links and lift over

dbSNP: rs680055; hg19: chr7-99457605;