19-15525386-C-G

Variant names:

• chr19-15525386-C-G
• NM_173483.4:c.50C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173483.4(CYP4F22):​c.50C>G​(p.Thr17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T17T) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CYP4F22 NM_173483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.02

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F22	NM_173483.4	c.50C>G	p.Thr17Arg	missense_variant	Exon 3 of 14	ENST00000269703.8	NP_775754.2
CYP4F22	XM_011527692.3	c.50C>G	p.Thr17Arg	missense_variant	Exon 4 of 15		XP_011525994.1
CYP4F22	XM_011527693.3	c.50C>G	p.Thr17Arg	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.50C>G	p.Thr17Arg	missense_variant	Exon 3 of 14	2	NM_173483.4	ENSP00000269703.1
CYP4F22	ENST00000601005.2	c.50C>G	p.Thr17Arg	missense_variant	Exon 1 of 12	5		ENSP00000469866.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461776 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 727202

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Aug 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.50C>G (p.T17R) alteration is located in exon 3 (coding exon 1) of the CYP4F22 gene. This alteration results from a C to G substitution at nucleotide position 50, causing the threonine (T) at amino acid position 17 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.070	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.21
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.4	N;.
REVEL	Uncertain	0.43
Sift	Benign	0.048	D;.
Sift4G	Benign	0.12	T;T
Polyphen		0.97	D;D
Vest4		0.48
MVP		0.40
MPC		0.89
ClinPred		0.63	D
GERP RS		3.7
Varity_R		0.16
gMVP		0.90

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: chr19-15636197;