chr1-47033313-T-G

Variant summary

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

The NM_178033.2(CYP4X1):ā€‹c.437T>Gā€‹(p.Phe146Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

CYP4X1
NM_178033.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.71
Variant links:
Genes affected
CYP4X1 (HGNC:20244): (cytochrome P450 family 4 subfamily X member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes and is located within a cluster of genes belonging to this superfamily on chromosome 1. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The expression pattern of a similar rat protein suggests that this protein may be involved in neurovascular function in the brain. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

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=0.3925453).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CYP4X1NM_178033.2 linkuse as main transcriptc.437T>G p.Phe146Cys missense_variant 4/12 ENST00000371901.4 NP_828847.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CYP4X1ENST00000371901.4 linkuse as main transcriptc.437T>G p.Phe146Cys missense_variant 4/121 NM_178033.2 ENSP00000360968 P1Q8N118-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00000205
AC:
3
AN:
1461570
Hom.:
0
Cov.:
30
AF XY:
0.00000275
AC XY:
2
AN XY:
727090
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152232
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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
Bravo
AF:
0.00000378

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 GeneticsSep 15, 2021The c.437T>G (p.F146C) alteration is located in exon 4 (coding exon 4) of the CYP4X1 gene. This alteration results from a T to G substitution at nucleotide position 437, causing the phenylalanine (F) at amino acid position 146 to be replaced by a cysteine (C). 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
0.16
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Benign
0.22
T
Eigen
Benign
0.19
Eigen_PC
Benign
0.065
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.42
T
M_CAP
Benign
0.016
T
MetaRNN
Benign
0.39
T
MetaSVM
Benign
-0.56
T
MutationAssessor
Uncertain
2.5
M
MutationTaster
Benign
0.94
N;N
PrimateAI
Benign
0.25
T
PROVEAN
Uncertain
-3.4
D
REVEL
Benign
0.26
Sift
Uncertain
0.029
D
Sift4G
Uncertain
0.0040
D
Polyphen
0.78
P
Vest4
0.20
MutPred
0.69
Gain of methylation at K150 (P = 0.1137);
MVP
0.75
MPC
0.35
ClinPred
0.85
D
GERP RS
2.3
Varity_R
0.36
gMVP
0.57

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.

Other links and lift over

dbSNP: rs892404572; hg19: chr1-47498985; API