chr19-15650164-A-T
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000896.3(CYP4F3):c.899A>T(p.Asp300Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000229 in 1,614,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00016 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
CYP4F3
NM_000896.3 missense
NM_000896.3 missense
Scores
8
5
1
Clinical Significance
Conservation
PhyloP100: 6.68
Genes affected
CYP4F3 (HGNC:2646): (cytochrome P450 family 4 subfamily F member 3) This gene, CYP4F3, 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. The enzyme starts the process of inactivating and degrading leukotriene B4, a potent mediator of inflammation. This gene is part of a cluster of cytochrome P450 genes on chromosome 19. Another member of this family, CYP4F8, is approximately 18 kb away. Several transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2019]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.941
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CYP4F3 | NM_000896.3 | c.899A>T | p.Asp300Val | missense_variant | 7/13 | ENST00000221307.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CYP4F3 | ENST00000221307.13 | c.899A>T | p.Asp300Val | missense_variant | 7/13 | 1 | NM_000896.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000164 AC: 25AN: 152164Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251248Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135850
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461878Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727240
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GnomAD4 genome ? AF: 0.000164 AC: 25AN: 152282Hom.: 0 Cov.: 31 AF XY: 0.000201 AC XY: 15AN XY: 74446
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 22, 2023 | The c.899A>T (p.D300V) alteration is located in exon 7 (coding exon 6) of the CYP4F3 gene. This alteration results from a A to T substitution at nucleotide position 899, causing the aspartic acid (D) at amino acid position 300 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H;H;H;H
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D;D;D
Polyphen
0.99
.;.;D;.
Vest4
MVP
MPC
0.29
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at