Genetic Variant FOXQ1:p.Thr60Lys (chr6-1312883-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033260.4(FOXQ1):c.179C>A(p.Thr60Lys) 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. 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. T60M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 35)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FOXQ1
NM_033260.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.197

Publications

0 publications found

Variant links:

Genes affected

FOXQ1 (HGNC:20951): (forkhead box Q1) FOXQ1 is a member of the FOX gene family, which is characterized by a conserved 110-amino acid DNA-binding motif called the forkhead or winged helix domain. FOX genes are involved in embryonic development, cell cycle regulation, tissue-specific gene expression, cell signaling, and tumorigenesis (Bieller et al., 2001 [PubMed 11747606]).[supplied by OMIM, May 2009]

FOXQ1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044857502).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033260.4. 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
	FOXQ1	NM_033260.4	MANE Select	c.179C>A	p.Thr60Lys	missense	Exon 1 of 1	NP_150285.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FOXQ1	ENST00000296839.5	TSL:6 MANE Select	c.179C>A	p.Thr60Lys	missense	Exon 1 of 1	ENSP00000296839.2	Q9C009

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

4946

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1125196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

540212

African (AFR)

AF:

0.00

AC:

AN:

23122

American (AMR)

AF:

0.00

AC:

AN:

9156

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14822

East Asian (EAS)

AF:

0.00

AC:

AN:

26982

South Asian (SAS)

AF:

0.00

AC:

AN:

31098

European-Finnish (FIN)

AF:

0.00

AC:

AN:

25226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3114

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

946452

Other (OTH)

AF:

0.00

AC:

AN:

45224

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.1

(source)

DANN

Benign

0.77

DEOGEN2

Benign

0.058

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.17

M_CAP

Benign

0.0056

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

-0.20

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.61

REVEL

Benign

0.011

Sift

Benign

0.82

Sift4G

Benign

0.93

Polyphen

0.0010

Vest4

0.051

MutPred

0.29

Gain of ubiquitination at T60 (P = 0.0025)

MVP

0.076

ClinPred

0.013

GERP RS

-2.4

Varity_R

0.038

gMVP

0.14

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over