rs118091316

Variant names:

• chr19-15525513-C-A
• NM_173483.4:c.177C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-15525513-C-A
• chr19-15525513-C-G
• chr19-15525513-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_173483.4(CYP4F22):​c.177C>A​(p.Phe59Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. F59F) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP4F22 NM_173483.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.06

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.962

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F22	NM_173483.4	c.177C>A	p.Phe59Leu	missense_variant	Exon 3 of 14	ENST00000269703.8	NP_775754.2
CYP4F22	XM_011527692.3	c.177C>A	p.Phe59Leu	missense_variant	Exon 4 of 15		XP_011525994.1
CYP4F22	XM_011527693.3	c.177C>A	p.Phe59Leu	missense_variant	Exon 3 of 14		XP_011525995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F22	ENST00000269703.8	c.177C>A	p.Phe59Leu	missense_variant	Exon 3 of 14	2	NM_173483.4	ENSP00000269703.1
CYP4F22	ENST00000601005.2	c.177C>A	p.Phe59Leu	missense_variant	Exon 1 of 12	5		ENSP00000469866.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459876 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 726336

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.95	.;D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.96	D;D
MetaSVM	Uncertain	0.23	D
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-5.1	D;.
REVEL	Pathogenic	0.70
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.83
MutPred		0.83		Gain of catalytic residue at F59 (P = 0.0045);Gain of catalytic residue at F59 (P = 0.0045);
MVP		0.94
MPC		0.87
ClinPred		1.0	D
GERP RS		3.8
Varity_R		0.82
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-15636324;