19-15529728-G-T

Variant names:

• chr19-15529728-G-T
• rs369811073
• NM_173483.4:c.242G>T

Variant summary

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

The NM_173483.4(CYP4F22):​c.242G>T​(p.Gly81Val) variant causes a missense change. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP4F22 NM_173483.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.45

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, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F22	NM_173483.4	c.242G>T	p.Gly81Val	missense_variant	Exon 4 of 14	ENST00000269703.8	NP_775754.2
CYP4F22	XM_011527692.3	c.242G>T	p.Gly81Val	missense_variant	Exon 5 of 15		XP_011525994.1
CYP4F22	XM_011527693.3	c.242G>T	p.Gly81Val	missense_variant	Exon 4 of 14		XP_011525995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F22	ENST00000269703.8	c.242G>T	p.Gly81Val	missense_variant	Exon 4 of 14	2	NM_173483.4	ENSP00000269703.1
CYP4F22	ENST00000601005.2	c.242G>T	p.Gly81Val	missense_variant	Exon 2 of 12	5		ENSP00000469866.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.075	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Pathogenic	0.83	D
MutationAssessor	Benign	1.9	L;L
PrimateAI	Uncertain	0.50	T
PROVEAN	Pathogenic	-6.9	D;.
REVEL	Pathogenic	0.72
Sift	Benign	0.067	T;.
Sift4G	Uncertain	0.032	D;D
Polyphen		0.90	P;P
Vest4		0.55
MVP		0.94
MPC		0.84
ClinPred		0.93	D
GERP RS		5.4
Varity_R		0.82
gMVP		0.77

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: rs369811073; hg19: chr19-15640539;