dbSNP rs760812037: FOXK1:p.Pro43Thr (chr7-4682435-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037165.2(FOXK1):c.127C>A(p.Pro43Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign 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. P43S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXK1
NM_001037165.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Publications

0 publications found

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]

FOXK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13725632).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037165.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXK1	NM_001037165.2	MANE Select	c.127C>A	p.Pro43Thr	missense	Exon 1 of 9	NP_001032242.1	P85037-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXK1	ENST00000328914.5	TSL:2 MANE Select	c.127C>A	p.Pro43Thr	missense	Exon 1 of 9	ENSP00000328720.4	P85037-1
	FOXK1	ENST00000937603.1		c.127C>A	p.Pro43Thr	missense	Exon 1 of 8	ENSP00000607662.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

835162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

386010

African (AFR)

AF:

0.00

AC:

AN:

15800

American (AMR)

AF:

0.00

AC:

AN:

1020

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5174

East Asian (EAS)

AF:

0.00

AC:

AN:

3682

South Asian (SAS)

AF:

0.00

AC:

AN:

17304

European-Finnish (FIN)

AF:

0.00

AC:

AN:

288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1622

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

762926

Other (OTH)

AF:

0.00

AC:

AN:

27346

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.0034

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.041

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.28

M_CAP

Pathogenic

0.66

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.33

MutationAssessor

Benign

0.20

PhyloP100

1.1

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.15

REVEL

Benign

0.24

Sift

Benign

0.30

Sift4G

Benign

0.72

Polyphen

0.22

Vest4

0.13

MutPred

0.27

Gain of phosphorylation at P43 (P = 0.0037)

MVP

0.58

MPC

2.1

ClinPred

0.21

GERP RS

-1.7

PromoterAI

0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.032

gMVP

0.22

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over