Genetic Variant NM_001037165.2:c.711G>A (chr7-4740988-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001037165.2(FOXK1):c.711G>A(p.Met237Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000129 in 1,555,136 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FOXK1
NM_001037165.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Publications

0 publications found

Variant links:

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]

FOXK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.066717595).

BS2

High AC in GnomAd4 at 6 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.711G>A	p.Met237Ile	missense	Exon 2 of 9	NP_001032242.1	P85037-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXK1	ENST00000328914.5	TSL:2 MANE Select	c.711G>A	p.Met237Ile	missense	Exon 2 of 9	ENSP00000328720.4	P85037-1
FOXK1	ENST00000460979.2	TSL:2	c.129G>A	p.Met43Ile	missense	Exon 1 of 2	ENSP00000475486.1	U3KQ26
FOXK1	ENST00000937603.1		c.561-13471G>A		intron	N/A	ENSP00000607662.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000203

AC:

AN:

197146

AF XY:

0.00000921

show subpopulations

Gnomad AFR exome

AF:

0.000335

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000998

AC:

AN:

1402952

Hom.:

Cov.:

AF XY:

0.00000717

AC XY:

AN XY:

697238

show subpopulations

African (AFR)

AF:

0.000170

AC:

AN:

29330

American (AMR)

AF:

0.00

AC:

AN:

32512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24598

East Asian (EAS)

AF:

0.00

AC:

AN:

33576

South Asian (SAS)

AF:

0.0000128

AC:

AN:

77836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52940

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5606

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1088692

Other (OTH)

AF:

0.000121

AC:

AN:

57862

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152184

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.533

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Benign

0.042

MetaRNN

Benign

0.067

MetaSVM

Benign

-0.40

MutationAssessor

Benign

1.4

PhyloP100

4.0

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.44

REVEL

Benign

0.19

Sift

Uncertain

0.018

Sift4G

Benign

0.10

Polyphen

0.0020

Vest4

0.16

MutPred

0.21

Gain of glycosylation at S236 (P = 0.0414)

MVP

0.42

MPC

0.61

ClinPred

0.089

GERP RS

1.9

PromoterAI

-0.0068

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.13

Mutation Taster

=83/17

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over