NM_001037165.2:c.155C>T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001037165.2(FOXK1):​c.155C>T​(p.Pro52Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 981,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000066 ( 0 hom. )

Consequence

FOXK1
NM_001037165.2 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0710
Variant links:
Genes affected
FOXK1 (HGNC:23480): (forkhead box K1) Enables 14-3-3 protein binding activity; DNA-binding transcription repressor activity, RNA polymerase II-specific; and transcription cis-regulatory region binding activity. Involved in several processes, including cellular glucose homeostasis; negative regulation of autophagy; and regulation of transcription, DNA-templated. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.23671964).
BS2
High AC in GnomAdExome4 at 55 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXK1NM_001037165.2 linkc.155C>T p.Pro52Leu missense_variant Exon 1 of 9 ENST00000328914.5 NP_001032242.1 P85037-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FOXK1ENST00000328914.5 linkc.155C>T p.Pro52Leu missense_variant Exon 1 of 9 2 NM_001037165.2 ENSP00000328720.4 P85037-1

Frequencies

GnomAD3 genomes
AF:
0.0000274
AC:
4
AN:
145924
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000608
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000658
AC:
55
AN:
835902
Hom.:
0
Cov.:
30
AF XY:
0.0000646
AC XY:
25
AN XY:
386762
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000694
Gnomad4 OTH exome
AF:
0.0000730
GnomAD4 genome
AF:
0.0000274
AC:
4
AN:
145924
Hom.:
0
Cov.:
31
AF XY:
0.0000423
AC XY:
3
AN XY:
70958
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000608
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000529

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 06, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.155C>T (p.P52L) alteration is located in exon 1 (coding exon 1) of the FOXK1 gene. This alteration results from a C to T substitution at nucleotide position 155, causing the proline (P) at amino acid position 52 to be replaced by a leucine (L). 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
0.10
BayesDel_addAF
Benign
-0.046
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
9.0
DANN
Uncertain
0.98
DEOGEN2
Benign
0.044
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.0015
N
LIST_S2
Benign
0.36
T
M_CAP
Pathogenic
0.59
D
MetaRNN
Benign
0.24
T
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
0.34
N
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
0.13
N
REVEL
Benign
0.24
Sift
Pathogenic
0.0
D
Sift4G
Uncertain
0.031
D
Polyphen
0.0
B
Vest4
0.18
MutPred
0.37
Loss of glycosylation at P52 (P = 0.0022);
MVP
0.58
MPC
1.9
ClinPred
0.20
T
GERP RS
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6
Varity_R
0.044
gMVP
0.18

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

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

Other links and lift over

dbSNP: rs1247787079; hg19: chr7-4722094; API