Variant 1-46933979-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000778.4(CYP4A11):c.1189G>T(p.Val397Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CYP4A11
NM_000778.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.75

Variant links:

Genes affected

CYP4A11 (HGNC:2642): (cytochrome P450 family 4 subfamily A member 11) 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 protein localizes to the endoplasmic reticulum and hydroxylates medium-chain fatty acids such as laurate and myristate. Multiple transcript variants have been found for this gene. [provided by RefSeq, Jan 2016]

CYP4A11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4A11	NM_000778.4 link	c.1189G>T	p.Val397Phe	missense_variant	9/12	ENST00000310638.9	NP_000769.2	Q02928-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4A11	ENST00000310638.9 link	c.1189G>T	p.Val397Phe	missense_variant	9/12	1	NM_000778.4	ENSP00000311095.4		Q02928-1
CYP4A11	ENST00000465874.5 link	n.635G>T		non_coding_transcript_exon_variant	6/8	2		ENSP00000476368.1		V9GY41

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 16, 2022

The c.1189G>T (p.V397F) alteration is located in exon 9 (coding exon 9) of the CYP4A11 gene. This alteration results from a G to T substitution at nucleotide position 1189, causing the valine (V) at amino acid position 397 to be replaced by a phenylalanine (F). 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

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

4.3

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

D;.;.;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.086

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Benign

-0.46

MutationAssessor

Benign

2.0

M;.;.;.

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-3.7

D;D;.;D

REVEL

Uncertain

0.37

Sift

Uncertain

0.0060

D;D;.;D

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

0.87

P;.;.;.

Vest4

0.36

MutPred

0.61

Loss of glycosylation at T395 (P = 0.1707);.;.;Loss of glycosylation at T395 (P = 0.1707);

MVP

0.55

MPC

0.35

ClinPred

0.89

GERP RS

-7.4

Varity_R

0.38

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over