rs1555730246

Positions:

• chr19-15548182-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_173483.4(CYP4F22):​c.1211T>C​(p.Leu404Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP4F22 NM_173483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.22

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.755

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP4F22	NM_173483.4	c.1211T>C	p.Leu404Pro	missense_variant	11/14	ENST00000269703.8	NP_775754.2
CYP4F22	XM_011527692.3	c.1211T>C	p.Leu404Pro	missense_variant	12/15		XP_011525994.1
CYP4F22	XM_011527693.3	c.1211T>C	p.Leu404Pro	missense_variant	11/14		XP_011525995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP4F22	ENST00000269703.8	c.1211T>C	p.Leu404Pro	missense_variant	11/14	2	NM_173483.4	ENSP00000269703	P1
CYP4F22	ENST00000601005.2	c.1211T>C	p.Leu404Pro	missense_variant	9/12	5		ENSP00000469866	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Atopic eczema;C0020757:Ichthyosis Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Jan 01, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Benign	19
DANN	Benign	0.94
DEOGEN2	Benign	0.095	T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.75	.;T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.75	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.6	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Uncertain	0.39
Sift	Benign	0.17	T;.
Sift4G	Benign	0.28	T;T
Polyphen		0.0020	B;B
Vest4		0.88
MutPred		0.58		Gain of disorder (P = 0.0123);Gain of disorder (P = 0.0123);
MVP		0.57
MPC		1.0
ClinPred		0.33	T
GERP RS		4.2
Varity_R		0.68
gMVP		0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1555730246; hg19: chr19-15658993;