7-4740929-C-G

Variant summary

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

The NM_001037165.2(FOXK1):​c.652C>G​(p.Leu218Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000488 in 1,433,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

FOXK1
NM_001037165.2 missense

Scores

7
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95
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=0.22497049).
BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXK1NM_001037165.2 linkc.652C>G p.Leu218Val missense_variant Exon 2 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.652C>G p.Leu218Val missense_variant Exon 2 of 9 2 NM_001037165.2 ENSP00000328720.4 P85037-1
FOXK1ENST00000460979.2 linkc.70C>G p.Leu24Val missense_variant Exon 1 of 2 2 ENSP00000475486.1 U3KQ26

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000445
AC:
1
AN:
224500
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
122344
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000962
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000488
AC:
7
AN:
1433976
Hom.:
0
Cov.:
34
AF XY:
0.00000421
AC XY:
3
AN XY:
713016
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:
0.00000636
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 15, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.652C>G (p.L218V) alteration is located in exon 2 (coding exon 2) of the FOXK1 gene. This alteration results from a C to G substitution at nucleotide position 652, causing the leucine (L) at amino acid position 218 to be replaced by a valine (V). 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
0.14
BayesDel_addAF
Uncertain
0.016
T
BayesDel_noAF
Benign
-0.21
CADD
Benign
20
DANN
Benign
0.85
DEOGEN2
Benign
0.051
T
Eigen
Benign
0.076
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.87
D
M_CAP
Uncertain
0.10
D
MetaRNN
Benign
0.22
T
MetaSVM
Uncertain
0.39
D
MutationAssessor
Benign
0.65
N
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.17
N
REVEL
Uncertain
0.37
Sift
Benign
0.69
T
Sift4G
Benign
1.0
T
Polyphen
0.82
P
Vest4
0.40
MutPred
0.14
Loss of glycosylation at P217 (P = 0.0933);
MVP
0.64
MPC
0.56
ClinPred
0.22
T
GERP RS
5.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.10
gMVP
0.38

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: rs775182634; hg19: chr7-4780560; API