NM_007253.4:c.251A>T

Variant names:

• chr19-15618052-A-T
• rs1568381738
• NM_007253.4:c.251A>T

Variant summary

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

The NM_007253.4(CYP4F8):​c.251A>T​(p.Tyr84Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 9/13 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y84C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CYP4F8 NM_007253.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282

Genes affected

CYP4F8 (HGNC:2648): (cytochrome P450 family 4 subfamily F member 8) This gene, CYP4F8, 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 protein localizes to the endoplasmic reticulum and functions as a 19-hydroxylase of prostaglandins in seminal vesicles. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F3, is approximately 18 kb away. [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
CYP4F8	NM_007253.4	c.251A>T	p.Tyr84Phe	missense_variant	Exon 3 of 13	ENST00000612078.5	NP_009184.1
CYP4F8	XM_024451341.2	c.251A>T	p.Tyr84Phe	missense_variant	Exon 3 of 11		XP_024307109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F8	ENST00000612078.5	c.251A>T	p.Tyr84Phe	missense_variant	Exon 3 of 13	1	NM_007253.4	ENSP00000477567.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.0054	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	5.3
DANN	Benign	0.15
DEOGEN2	Benign	0.069	.;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.84	T;T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.81	T;T
Polyphen		0.0040	.;B
Vest4		0.18
MutPred		0.85		.;Loss of catalytic residue at Y84 (P = 0.2764);
MVP		0.10
ClinPred		0.24	T
GERP RS		-0.39
Varity_R		0.12
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1568381738; hg19: chr19-15728863;