NM_001037165.2:c.127C>T

Variant names:

• chr7-4682435-C-T
• rs760812037
• NM_001037165.2:c.127C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001037165.2(FOXK1):​c.127C>T​(p.Pro43Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000283 in 981,060 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 𝑓 0.00060 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00023 (1 hom.)
• Consequence: FOXK1 NM_001037165.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.07
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029079705).
• BS2: High AC in GnomAd4 at 88 AD gene.

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>T	p.Pro43Ser	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>T	p.Pro43Ser	missense	Exon 1 of 9	ENSP00000328720.4	P85037-1
	FOXK1	ENST00000937603.1		c.127C>T	p.Pro43Ser	missense	Exon 1 of 8	ENSP00000607662.1

Frequencies

GnomAD3 genomes AF: 0.000603 AC: 88 AN: 145898 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000681

Gnomad ASJ AF: 0.00266

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000242

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00114

Gnomad OTH AF: 0.000500

GnomAD2 exomes AF: 0.00 AC: 0 AN: 6 AF XY: 0.00

Gnomad NFE exome AF: 0.00

GnomAD4 exome AF: 0.000228 AC: 190 AN: 835162 Hom.: 1 Cov.: 30 AF XY: 0.000205 AC XY: 79 AN XY: 386010

African (AFR) AF: 0.00 AC: 0 AN: 15800

American (AMR) AF: 0.00 AC: 0 AN: 1020

Ashkenazi Jewish (ASJ) AF: 0.00290 AC: 15 AN: 5174

East Asian (EAS) AF: 0.00 AC: 0 AN: 3682

South Asian (SAS) AF: 0.00 AC: 0 AN: 17304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 288

Middle Eastern (MID) AF: 0.000617 AC: 1 AN: 1622

European-Non Finnish (NFE) AF: 0.000223 AC: 170 AN: 762926

Other (OTH) AF: 0.000146 AC: 4 AN: 27346

GnomAD4 genome AF: 0.000603 AC: 88 AN: 145898 Hom.: 0 Cov.: 31 AF XY: 0.000536 AC XY: 38 AN XY: 70952

African (AFR) AF: 0.00 AC: 0 AN: 40768

American (AMR) AF: 0.0000681 AC: 1 AN: 14688

Ashkenazi Jewish (ASJ) AF: 0.00266 AC: 9 AN: 3388

East Asian (EAS) AF: 0.00 AC: 0 AN: 5046

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.000242 AC: 2 AN: 8274

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.00114 AC: 75 AN: 65712

Other (OTH) AF: 0.000500 AC: 1 AN: 2000

Alfa AF: 0.000583 Hom.: 0

Bravo AF: 0.000506

ExAC AF: 0.00211 AC: 2

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	0.092
BayesDel_addAF	Benign	-0.00077	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.29	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.38	T
MutationAssessor	Benign	0.55	N
PhyloP100		1.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-0.080	N
REVEL	Benign	0.25
Sift	Benign	0.50	T
Sift4G	Benign	0.86	T
Polyphen		0.12	B
Vest4		0.13
MutPred		0.23		Gain of phosphorylation at P43 (P = 0.0056)
MVP		0.57
MPC		1.9
ClinPred		0.12	T
GERP RS		-1.7
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.019
gMVP		0.18
Mutation Taster		=94/6	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: rs760812037; hg19: chr7-4722066;