rs760727576

chr19-15544207-C-Gchr19-15544207-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_173483.4(CYP4F22):c.1064C>G(p.Pro355Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P355L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP4F22 NM_173483.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP4F22	NM_173483.4	c.1064C>G	p.Pro355Arg	missense_variant	10/14	ENST00000269703.8
CYP4F22	XM_011527692.3	c.1064C>G	p.Pro355Arg	missense_variant	11/15
CYP4F22	XM_011527693.3	c.1064C>G	p.Pro355Arg	missense_variant	10/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CYP4F22	ENST00000269703.8	c.1064C>G	p.Pro355Arg	missense_variant	10/14	2	NM_173483.4	P1
CYP4F22	ENST00000601005.2	c.1064C>G	p.Pro355Arg	missense_variant	8/12	5		P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T;T
Eigen	Uncertain	0.32
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.71	D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	0.22	D
MutationAssessor	Pathogenic	3.0	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-6.1	D;.
REVEL	Uncertain	0.55
Sift	Uncertain	0.0070	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.91	P;P
Vest4		0.58
MutPred		0.75		Gain of MoRF binding (P = 0.05);Gain of MoRF binding (P = 0.05);
MVP		0.85
MPC		0.85
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.80
gMVP		0.86

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

Other links and lift over

dbSNP: rs760727576; hg19: chr19-15655018;