7-4740988-G-C

Variant names:

• chr7-4740988-G-C
• rs367560933
• NM_001037165.2:c.711G>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.711G>C​(p.Met237Ile) variant causes a missense change. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FOXK1 NM_001037165.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.97
• 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=0.103734076).

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.711G>C	p.Met237Ile	missense	Exon 2 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.711G>C	p.Met237Ile	missense	Exon 2 of 9	ENSP00000328720.4	P85037-1
	FOXK1	ENST00000460979.2	TSL:2	c.129G>C	p.Met43Ile	missense	Exon 1 of 2	ENSP00000475486.1	U3KQ26
	FOXK1	ENST00000937603.1		c.561-13471G>C		intron	N/A	ENSP00000607662.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.20
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.19
Sift	Uncertain	0.018	D
Sift4G	Benign	0.10	T
Polyphen		0.0020	B
Vest4		0.16
MutPred		0.21		Gain of glycosylation at S236 (P = 0.0414)
MVP		0.43
MPC		0.61
ClinPred		0.28	T
GERP RS		1.9
PromoterAI		0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.13
Mutation Taster		=83/17	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: rs367560933; hg19: chr7-4780619;