19-15525499-C-T

Variant summary

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

The NM_173483.4(CYP4F22):​c.163C>T​(p.Arg55Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,258 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

CYP4F22
NM_173483.4 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.887
Variant links:
Genes affected
CYP4F22 (HGNC:26820): (cytochrome P450 family 4 subfamily F member 22) 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 19 and encodes an enzyme thought to play a role in the 12(R)-lipoxygenase pathway. Mutations in this gene are the cause of ichthyosis lamellar type 3. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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 rank MANE Protein UniProt
CYP4F22NM_173483.4 linkc.163C>T p.Arg55Trp missense_variant Exon 3 of 14 ENST00000269703.8 NP_775754.2 Q6NT55
CYP4F22XM_011527692.3 linkc.163C>T p.Arg55Trp missense_variant Exon 4 of 15 XP_011525994.1 Q6NT55
CYP4F22XM_011527693.3 linkc.163C>T p.Arg55Trp missense_variant Exon 3 of 14 XP_011525995.1 Q6NT55

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP4F22ENST00000269703.8 linkc.163C>T p.Arg55Trp missense_variant Exon 3 of 14 2 NM_173483.4 ENSP00000269703.1 Q6NT55
CYP4F22ENST00000601005.2 linkc.163C>T p.Arg55Trp missense_variant Exon 1 of 12 5 ENSP00000469866.1 Q6NT55

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD3 exomes
AF:
0.0000279
AC:
7
AN:
250566
Hom.:
0
AF XY:
0.0000369
AC XY:
5
AN XY:
135488
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.0000472
Gnomad NFE exome
AF:
0.00000882
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000137
AC:
20
AN:
1461046
Hom.:
0
Cov.:
32
AF XY:
0.00000963
AC XY:
7
AN XY:
726856
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.00000899
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152212
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74354
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
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:
0.0000388
Hom.:
0
Bravo
AF:
0.0000227
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 02, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.163C>T (p.R55W) alteration is located in exon 3 (coding exon 1) of the CYP4F22 gene. This alteration results from a C to T substitution at nucleotide position 163, causing the arginine (R) at amino acid position 55 to be replaced by a tryptophan (W). 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
-0.046
T
BayesDel_noAF
Benign
-0.12
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;T
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.15
FATHMM_MKL
Uncertain
0.82
D
LIST_S2
Uncertain
0.91
.;D
M_CAP
Uncertain
0.098
D
MetaRNN
Uncertain
0.62
D;D
MetaSVM
Uncertain
-0.072
T
MutationAssessor
Uncertain
2.3
M;M
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-5.2
D;.
REVEL
Uncertain
0.41
Sift
Uncertain
0.015
D;.
Sift4G
Benign
0.066
T;T
Polyphen
0.037
B;B
Vest4
0.53
MVP
0.57
MPC
0.47
ClinPred
0.85
D
GERP RS
3.8
Varity_R
0.17
gMVP
0.67

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: rs750733757; hg19: chr19-15636310; API