rs1247787079

Variant names:

• chr7-4682463-C-G
• NM_001037165.2:c.155C>G

Your query was ambiguous. Multiple possible variants found:

• chr7-4682463-C-G
• chr7-4682463-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037165.2(FOXK1):​c.155C>G​(p.Pro52Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000012 in 835,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. P52L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: FOXK1 NM_001037165.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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

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=0.21167898).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXK1	NM_001037165.2	c.155C>G	p.Pro52Arg	missense_variant	Exon 1 of 9	ENST00000328914.5	NP_001032242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXK1	ENST00000328914.5	c.155C>G	p.Pro52Arg	missense_variant	Exon 1 of 9	2	NM_001037165.2	ENSP00000328720.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000120 AC: 1 AN: 835902 Hom.: 0 Cov.: 30 AF XY: 0.00000259 AC XY: 1 AN XY: 386762

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: 0.00000131

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.077	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	14
DANN	Benign	0.95
DEOGEN2	Benign	0.045	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0038	N
LIST_S2	Benign	0.26	T
M_CAP	Pathogenic	0.52	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.034	D
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.38		Loss of glycosylation at P52 (P = 0.0022);
MVP		0.43
MPC		2.0
ClinPred		0.094	T
GERP RS		0.50
Varity_R		0.070
gMVP		0.17

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-4722094;