Variant 1-47084862-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_178134.3(CYP4Z1):c.656G>A(p.Ser219Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 1,522,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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 0.000013 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

CYP4Z1
NM_178134.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0960

Variant links:

Genes affected

CYP4Z1 (HGNC:20583): (cytochrome P450 family 4 subfamily Z member 1) 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. This gene is part of a cluster of cytochrome P450 genes on chromosome 1p33. [provided by RefSeq, Jul 2008]

CYP4Z1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.107457936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4Z1	NM_178134.3 linkuse as main transcript	c.656G>A	p.Ser219Asn	missense_variant	6/12	ENST00000334194.4	NP_835235.1	Q86W10
CYP4Z1	XM_024453856.2 linkuse as main transcript	c.542G>A	p.Ser181Asn	missense_variant	7/13		XP_024309624.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4Z1	ENST00000334194.4 linkuse as main transcript	c.656G>A	p.Ser219Asn	missense_variant	6/12	1	NM_178134.3	ENSP00000334246.3		Q86W10

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000494

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1373400

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

674110

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000168

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72714

show subpopulations

Gnomad4 AFR

AF:

0.0000494

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 17, 2024

The c.656G>A (p.S219N) alteration is located in exon 6 (coding exon 6) of the CYP4Z1 gene. This alteration results from a G to A substitution at nucleotide position 656, causing the serine (S) at amino acid position 219 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.37

DANN

Benign

0.56

DEOGEN2

Benign

0.0066

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.20

M_CAP

Benign

0.015

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.90

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.54

REVEL

Benign

0.075

Sift

Benign

0.58

Sift4G

Benign

0.21

Polyphen

0.32

Vest4

0.095

MutPred

0.62

Loss of loop (P = 0.1242);

MVP

0.21

MPC

1.2

ClinPred

0.16

GERP RS

-4.4

Varity_R

0.094

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over