1-47068740-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_178134.3(CYP4Z1):​c.296C>T​(p.Ala99Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,461,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

CYP4Z1
NM_178134.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.697
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.32221457).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP4Z1NM_178134.3 linkc.296C>T p.Ala99Val missense_variant 2/12 ENST00000334194.4 NP_835235.1 Q86W10
CYP4Z1XM_024453856.2 linkc.182C>T p.Ala61Val missense_variant 3/13 XP_024309624.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP4Z1ENST00000334194.4 linkc.296C>T p.Ala99Val missense_variant 2/121 NM_178134.3 ENSP00000334246.3 Q86W10

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251256
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135776
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000981
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000465
AC:
68
AN:
1461758
Hom.:
0
Cov.:
31
AF XY:
0.0000385
AC XY:
28
AN XY:
727178
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:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000576
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000501
Hom.:
0
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

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 submitterclinical testingAmbry GeneticsNov 08, 2022The c.296C>T (p.A99V) alteration is located in exon 2 (coding exon 2) of the CYP4Z1 gene. This alteration results from a C to T substitution at nucleotide position 296, causing the alanine (A) at amino acid position 99 to be replaced by a valine (V). 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
Benign
0.13
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
15
DANN
Benign
0.74
DEOGEN2
Benign
0.020
T
Eigen
Benign
-0.41
Eigen_PC
Benign
-0.47
FATHMM_MKL
Benign
0.52
D
LIST_S2
Benign
0.53
T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.32
T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.67
N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.19
Sift
Benign
0.64
T
Sift4G
Benign
1.0
T
Polyphen
0.88
P
Vest4
0.47
MVP
0.29
MPC
0.048
ClinPred
0.094
T
GERP RS
2.8
Varity_R
0.053
gMVP
0.24

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

LitVar

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

Other links and lift over

dbSNP: rs373456415; hg19: chr1-47534412; API