rs142720535

Variant names:

• chr19-15525458-G-C
• rs142720535
• NM_173483.4:c.122G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-15525458-G-C
• chr19-15525458-G-A
• chr19-15525458-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_173483.4(CYP4F22):​c.122G>C​(p.Arg41Pro) 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 benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R41W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP4F22 NM_173483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.888
• Publications: 5 publications found

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]

CYP4F22 Gene-Disease associations (from GenCC):

• autosomal recessive congenital ichthyosis 5

  Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33486554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173483.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F22	NM_173483.4	MANE Select	c.122G>C	p.Arg41Pro	missense	Exon 3 of 14	NP_775754.2	Q6NT55

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP4F22	ENST00000269703.8	TSL:2 MANE Select	c.122G>C	p.Arg41Pro	missense	Exon 3 of 14	ENSP00000269703.1	Q6NT55
	CYP4F22	ENST00000601005.2	TSL:5	c.122G>C	p.Arg41Pro	missense	Exon 1 of 12	ENSP00000469866.1	Q6NT55
	CYP4F22	ENST00000894419.1		c.122G>C	p.Arg41Pro	missense	Exon 4 of 15	ENSP00000564478.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	2.4
DANN	Benign	0.80
DEOGEN2	Benign	0.29	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.025	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.89
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.066	T
Polyphen		0.033	B
Vest4		0.34
MutPred		0.66		Loss of MoRF binding (P = 8e-04)
MVP		0.23
MPC		0.34
ClinPred		0.31	T
GERP RS		-8.3
PromoterAI		0.012	Neutral
Varity_R		0.43
gMVP		0.85
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs142720535; hg19: chr19-15636269;