19-15540490-G-T

Variant names:

• chr19-15540490-G-T
• rs572278771
• NM_173483.4:c.712G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173483.4(CYP4F22):​c.712G>T​(p.Ala238Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP4F22 NM_173483.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.586

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15691233).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F22	NM_173483.4	c.712G>T	p.Ala238Ser	missense_variant	Exon 8 of 14	ENST00000269703.8	NP_775754.2
CYP4F22	XM_011527692.3	c.712G>T	p.Ala238Ser	missense_variant	Exon 9 of 15		XP_011525994.1
CYP4F22	XM_011527693.3	c.712G>T	p.Ala238Ser	missense_variant	Exon 8 of 14		XP_011525995.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F22	ENST00000269703.8	c.712G>T	p.Ala238Ser	missense_variant	Exon 8 of 14	2	NM_173483.4	ENSP00000269703.1
CYP4F22	ENST00000601005.2	c.712G>T	p.Ala238Ser	missense_variant	Exon 6 of 12	5		ENSP00000469866.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251372 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135890

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727242

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.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.84
DEOGEN2	Benign	0.033	T;T
Eigen	Benign	-0.82
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.085	N
LIST_S2	Benign	0.77	.;T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0050	N;N
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.58	N;.
REVEL	Benign	0.091
Sift	Benign	0.51	T;.
Sift4G	Benign	0.46	T;T
Polyphen		0.18	B;B
Vest4		0.21
MutPred		0.29		Gain of disorder (P = 0.0529);Gain of disorder (P = 0.0529);
MVP		0.50
MPC		0.23
ClinPred		0.24	T
GERP RS		4.3
Varity_R		0.079
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs572278771; hg19: chr19-15651301;