NM_057095.3:c.125C>A

Variant names:

• chr7-99836506-C-A
• rs1043237537
• NM_057095.3:c.125C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_057095.3(CYP3A43):​c.125C>A​(p.Thr42Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,194 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: CYP3A43 NM_057095.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11639947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP3A43	NM_057095.3	c.125C>A	p.Thr42Asn	missense_variant	Exon 2 of 13	ENST00000354829.7	NP_476436.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP3A43	ENST00000354829.7	c.125C>A	p.Thr42Asn	missense_variant	Exon 2 of 13	1	NM_057095.3	ENSP00000346887.3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152194 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74350

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.92
DEOGEN2	Benign	0.029	.;T;.;.;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0040	N
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.12	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	.;L;.;L;.;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.1	.;N;.;N;N;N;N
REVEL	Benign	0.036
Sift	Uncertain	0.019	.;D;.;T;T;D;D
Sift4G	Benign	0.13	T;T;T;T;T;T;T
Polyphen		0.015, 0.020	.;B;.;.;.;B;.
Vest4		0.25
MutPred		0.55		Loss of glycosylation at T42 (P = 0.0116);Loss of glycosylation at T42 (P = 0.0116);Loss of glycosylation at T42 (P = 0.0116);Loss of glycosylation at T42 (P = 0.0116);Loss of glycosylation at T42 (P = 0.0116);Loss of glycosylation at T42 (P = 0.0116);Loss of glycosylation at T42 (P = 0.0116);
MVP		0.088
MPC		0.039
ClinPred		0.66	D
GERP RS		-4.9
Varity_R		0.21
gMVP		0.56

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: rs1043237537; hg19: chr7-99434129;