7-4754469-T-C

Variant names:

• chr7-4754469-T-C
• rs1583210650
• NM_001037165.2:c.757T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001037165.2(FOXK1):​c.757T>C​(p.Ser253Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FOXK1 NM_001037165.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.757T>C	p.Ser253Pro	missense	Exon 3 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.757T>C	p.Ser253Pro	missense	Exon 3 of 9	ENSP00000328720.4	P85037-1
	FOXK1	ENST00000937603.1		c.571T>C	p.Ser191Pro	missense	Exon 2 of 8	ENSP00000607662.1
	FOXK1	ENST00000460979.2	TSL:2	c.175T>C	p.Ser59Pro	missense	Exon 2 of 2	ENSP00000475486.1	U3KQ26

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.51	D
BayesDel_noAF	Pathogenic	0.49
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Pathogenic	0.47	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		6.3
PrimateAI	Uncertain	0.73	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.50
MutPred		0.14		Loss of phosphorylation at S253 (P = 0.0344)
MVP		0.97
MPC		1.6
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.81
gMVP		0.79
Mutation Taster		=29/71	disease causing

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

Other links and lift over

dbSNP: rs1583210650; hg19: chr7-4794100;