Genetic Variant NM_057095.3:c.853A>G (chr7-99856887-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_057095.3(CYP3A43):c.853A>G(p.Lys285Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CYP3A43
NM_057095.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00400

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.042929173).

BP6

Variant 7-99856887-A-G is Benign according to our data. Variant chr7-99856887-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2554537.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_057095.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP3A43	NM_057095.3	MANE Select	c.853A>G	p.Lys285Glu	missense	Exon 9 of 13	NP_476436.1	Q9HB55-1
CYP3A43	NM_022820.5		c.853A>G	p.Lys285Glu	missense	Exon 9 of 13	NP_073731.1	Q9HB55-2
CYP3A43	NM_057096.4		c.853A>G	p.Lys285Glu	missense	Exon 9 of 12	NP_476437.1	Q9HB55-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CYP3A43	ENST00000354829.7	TSL:1 MANE Select	c.853A>G	p.Lys285Glu	missense	Exon 9 of 13	ENSP00000346887.3	Q9HB55-1
CYP3A43	ENST00000222382.5	TSL:1	c.853A>G	p.Lys285Glu	missense	Exon 9 of 13	ENSP00000222382.5	Q9HB55-2
CYP3A43	ENST00000312017.9	TSL:1	c.853A>G	p.Lys285Glu	missense	Exon 9 of 12	ENSP00000312110.5	Q9HB55-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

2.1

(source)

DANN

Benign

0.25

DEOGEN2

Benign

0.0087

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0051

LIST_S2

Benign

0.033

M_CAP

Benign

0.0092

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.94

PhyloP100

0.0040

PrimateAI

Benign

0.31

PROVEAN

Benign

1.3

REVEL

Benign

0.086

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.065

MutPred

0.54

Loss of ubiquitination at K285 (P = 0.0233)

MVP

0.33

MPC

0.028

ClinPred

0.035

GERP RS

1.3

Varity_R

0.038

gMVP

0.33

Mutation Taster

=98/2

polymorphism

(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

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over