6-1312925-C-G

Variant names:

• chr6-1312925-C-G
• rs1162969602
• NM_033260.4:c.221C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033260.4(FOXQ1):​c.221C>G​(p.Ala74Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000893 in 1,119,612 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. 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. A74V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.9e-7 (0 hom.)
• Consequence: FOXQ1 NM_033260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.144
• 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: 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=0.06657782).

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.221C>G	p.Ala74Gly	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.221C>G	p.Ala74Gly	missense	Exon 1 of 1	ENSP00000296839.2	Q9C009

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.93e-7 AC: 1 AN: 1119612 Hom.: 0 Cov.: 66 AF XY: 0.00000186 AC XY: 1 AN XY: 537754

African (AFR) AF: 0.0000437 AC: 1 AN: 22900

American (AMR) AF: 0.00 AC: 0 AN: 9222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14602

East Asian (EAS) AF: 0.00 AC: 0 AN: 26714

South Asian (SAS) AF: 0.00 AC: 0 AN: 28400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3104

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 943024

Other (OTH) AF: 0.00 AC: 0 AN: 44938

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.88
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.14
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.96	N
REVEL	Benign	0.026
Sift	Benign	0.12	T
Sift4G	Benign	0.41	T
Polyphen		0.057	B
Vest4		0.058
MutPred		0.19		Loss of glycosylation at P72 (P = 0.1643)
MVP		0.10
ClinPred		0.066	T
GERP RS		2.4
Varity_R		0.12
gMVP		0.10
Mutation Taster		=92/8	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: rs1162969602; hg19: chr6-1313160;