19-41121476-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000774.5(CYP2F1):​c.503C>A​(p.Thr168Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CYP2F1
NM_000774.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.871
Variant links:
Genes affected
CYP2F1 (HGNC:2632): (cytochrome P450 family 2 subfamily F member 1) 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 protein localizes to the endoplasmic reticulum and is known to dehydrogenate 3-methylindole, an endogenous toxin derived from the fermentation of tryptophan, as well as xenobiotic substrates such as naphthalene and ethoxycoumarin. This gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.21147284).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CYP2F1NM_000774.5 linkc.503C>A p.Thr168Lys missense_variant Exon 5 of 10 ENST00000331105.7 NP_000765.2 P24903-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CYP2F1ENST00000331105.7 linkc.503C>A p.Thr168Lys missense_variant Exon 5 of 10 1 NM_000774.5 ENSP00000333534.2 P24903-1
CYP2F1ENST00000532164.2 linkn.503C>A non_coding_transcript_exon_variant Exon 5 of 10 1 ENSP00000471416.1 P24903-2
CYP2F1ENST00000531409.5 linkn.578C>A non_coding_transcript_exon_variant Exon 5 of 8 2
CYP2F1ENST00000526093.5 linkn.225-481C>A intron_variant Intron 2 of 3 4

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000798
AC:
2
AN:
250472
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135414
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000546
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1459904
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726338
show subpopulations
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:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
30

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 20, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.503C>A (p.T168K) alteration is located in exon 5 (coding exon 4) of the CYP2F1 gene. This alteration results from a C to A substitution at nucleotide position 503, causing the threonine (T) at amino acid position 168 to be replaced by a lysine (K). 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
0.15
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
12
DANN
Benign
0.92
DEOGEN2
Benign
0.027
T
Eigen
Benign
-0.57
Eigen_PC
Benign
-0.65
FATHMM_MKL
Benign
0.088
N
LIST_S2
Benign
0.71
T
M_CAP
Benign
0.046
D
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.39
T
PROVEAN
Pathogenic
-4.8
D
REVEL
Benign
0.13
Sift
Uncertain
0.0070
D
Sift4G
Benign
0.12
T
Polyphen
0.53
P
Vest4
0.17
MutPred
0.65
Gain of methylation at T168 (P = 0.0101);
MVP
0.74
MPC
0.41
ClinPred
0.62
D
GERP RS
0.74
Varity_R
0.35
gMVP
0.61

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1288556893; hg19: chr19-41627381; API