6-1312733-C-G

Variant names:

• chr6-1312733-C-G
• rs566897925
• NM_033260.4:c.29C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_033260.4(FOXQ1):​c.29C>G​(p.Ala10Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000832 in 1,202,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. A10E) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: FOXQ1 NM_033260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12878597).

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.29C>G	p.Ala10Gly	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.29C>G	p.Ala10Gly	missense	Exon 1 of 1	ENSP00000296839.2	Q9C009

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.32e-7 AC: 1 AN: 1202512 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 586160

African (AFR) AF: 0.00 AC: 0 AN: 24272

American (AMR) AF: 0.00 AC: 0 AN: 12632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17776

East Asian (EAS) AF: 0.00 AC: 0 AN: 27666

South Asian (SAS) AF: 0.00 AC: 0 AN: 49066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4834

European-Non Finnish (NFE) AF: 0.00000101 AC: 1 AN: 988730

Other (OTH) AF: 0.00 AC: 0 AN: 48818

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.061	T
Eigen	Benign	-0.50
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.67	D
MetaRNN	Benign	0.13	T
MetaSVM	Uncertain	-0.20	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.10
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.20
Sift	Benign	0.19	T
Sift4G	Benign	0.35	T
Polyphen		0.0070	B
Vest4		0.13
MutPred		0.27		Gain of methylation at R9 (P = 0.0475)
MVP		0.64
ClinPred		0.20	T
GERP RS		2.9
Varity_R		0.11
gMVP		0.15
Mutation Taster		=99/1	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: rs566897925; hg19: chr6-1312968;