NM_021187.4:c.1064G>T

Variant names:

• chr19-15922088-C-A
• rs374693440
• NM_021187.4:c.1064G>T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_021187.4(CYP4F11):​c.1064G>T​(p.Arg355Leu) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R355Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CYP4F11 NM_021187.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.23

Genes affected

CYP4F11 (HGNC:13265): (cytochrome P450 family 4 subfamily F member 11) This gene, CYP4F11, 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. Another member of this family, CYP4F2, is approximately 16 kb away. Alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CYP4F11	NM_021187.4	c.1064G>T	p.Arg355Leu	missense_variant	Exon 8 of 12	ENST00000402119.9	NP_067010.3
CYP4F11	NM_001128932.2	c.1064G>T	p.Arg355Leu	missense_variant	Exon 9 of 13		NP_001122404.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CYP4F11	ENST00000402119.9	c.1064G>T	p.Arg355Leu	missense_variant	Exon 8 of 12	1	NM_021187.4	ENSP00000384588.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T;.;T;.
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.22
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	.;.;D;D;D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.84	D;D;D;D;D
MetaSVM	Uncertain	-0.094	T
MutationAssessor	Uncertain	2.9	.;M;.;M;.
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-6.3	D;D;.;D;.
REVEL	Uncertain	0.59
Sift	Uncertain	0.0010	D;D;.;D;.
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.85	P;P;P;P;.
Vest4		0.75
MutPred		0.60		Gain of catalytic residue at R355 (P = 0.0151);Gain of catalytic residue at R355 (P = 0.0151);Gain of catalytic residue at R355 (P = 0.0151);Gain of catalytic residue at R355 (P = 0.0151);.;
MVP		0.80
MPC		0.24
ClinPred		1.0	D
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.88
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs374693440; hg19: chr19-16032898;