7-4682534-G-C

Variant names:

• chr7-4682534-G-C
• rs1779764805
• NM_001037165.2:c.226G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037165.2(FOXK1):​c.226G>C​(p.Gly76Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: FOXK1 NM_001037165.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0400
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12536192).

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.226G>C	p.Gly76Arg	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.226G>C	p.Gly76Arg	missense	Exon 1 of 9	ENSP00000328720.4	P85037-1
	FOXK1	ENST00000937603.1		c.226G>C	p.Gly76Arg	missense	Exon 1 of 8	ENSP00000607662.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

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	Benign	0.23
BayesDel_addAF	Benign	-0.022	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.033	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.34	T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.073	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.040
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.86	N
REVEL	Benign	0.26
Sift	Benign	0.098	T
Sift4G	Benign	0.57	T
Polyphen		0.93	P
Vest4		0.20
MutPred		0.23		Gain of methylation at G76 (P = 0.0128)
MVP		0.42
MPC		2.2
ClinPred		0.22	T
GERP RS		-0.33
PromoterAI		0.078	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Varity_R		0.034
gMVP		0.17
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1779764805; hg19: chr7-4722165;