6-1312883-C-T

Variant summary

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

The NM_033260.4(FOXQ1):​c.179C>T​(p.Thr60Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000889 in 1,125,196 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T60P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 35)
Exomes 𝑓: 8.9e-7 ( 0 hom. )

Consequence

FOXQ1
NM_033260.4 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.197
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]

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=0.05265528).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FOXQ1NM_033260.4 linkc.179C>T p.Thr60Met 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
FOXQ1ENST00000296839.5 linkc.179C>T p.Thr60Met missense_variant Exon 1 of 1 6 NM_033260.4 ENSP00000296839.2 Q9C009

Frequencies

GnomAD3 genomes
Cov.:
35
GnomAD4 exome
AF:
8.89e-7
AC:
1
AN:
1125196
Hom.:
0
Cov.:
79
AF XY:
0.00
AC XY:
0
AN XY:
540212
show subpopulations
Gnomad4 AFR exome
AF:
0.0000432
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
35

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 09, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.179C>T (p.T60M) alteration is located in exon 1 (coding exon 1) of the FOXQ1 gene. This alteration results from a C to T substitution at nucleotide position 179, causing the threonine (T) at amino acid position 60 to be replaced by a methionine (M). 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
0.10
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
7.5
DANN
Benign
0.93
DEOGEN2
Benign
0.046
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.014
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.0059
T
MetaRNN
Benign
0.053
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.34
N
PrimateAI
Pathogenic
0.79
T
PROVEAN
Benign
-0.28
N
REVEL
Benign
0.015
Sift
Benign
0.24
T
Sift4G
Benign
0.13
T
Polyphen
0.030
B
Vest4
0.056
MutPred
0.19
Loss of phosphorylation at T60 (P = 0.0029);
MVP
0.11
ClinPred
0.038
T
GERP RS
-2.4
Varity_R
0.020
gMVP
0.15

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.

Other links and lift over

dbSNP: rs1465054050; hg19: chr6-1313118; API