Genetic Variant FOXQ1:p.Asp63Glu (chr6-1312893-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033260.4(FOXQ1):c.189C>A(p.Asp63Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000554 in 1,280,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000055 ( 0 hom. )

Consequence

FOXQ1
NM_033260.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.930

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004291445).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXQ1	NM_033260.4 link	c.189C>A	p.Asp63Glu	missense_variant	Exon 1 of 1	ENST00000296839.5	NP_150285.3	Q9C009

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXQ1	ENST00000296839.5 link	c.189C>A	p.Asp63Glu	missense_variant	Exon 1 of 1	6	NM_033260.4	ENSP00000296839.2		Q9C009

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151674

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000328

AC:

AN:

6094

Hom.:

AF XY:

0.000583

AC XY:

AN XY:

3428

show subpopulations

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 SAS exome

AF:

0.00272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000549

AC:

AN:

1128972

Hom.:

Cov.:

AF XY:

0.0000737

AC XY:

AN XY:

542644

show subpopulations

Gnomad4 AFR exome

AF:

0.0000432

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000370

Gnomad4 SAS exome

AF:

0.00153

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000211

Gnomad4 OTH exome

AF:

0.000198

GnomAD4 genome

AF:

0.0000593

AC:

AN:

151782

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

ExAC

AF:

0.000371

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 21, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.189C>A (p.D63E) alteration is located in exon 1 (coding exon 1) of the FOXQ1 gene. This alteration results from a C to A substitution at nucleotide position 189, causing the aspartic acid (D) at amino acid position 63 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.037

DANN

Benign

0.74

DEOGEN2

Benign

0.059

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.18

M_CAP

Benign

0.0022

MetaRNN

Benign

0.0043

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.50

REVEL

Benign

0.024

Sift

Benign

0.71

Sift4G

Benign

0.71

Polyphen

0.10

Vest4

0.037

MutPred

0.18

Loss of glycosylation at T60 (P = 0.2018);

MVP

0.095

ClinPred

0.019

GERP RS

-2.5

Varity_R

0.029

gMVP

0.050

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over