X-71101060-A-C

Variant names:

• chrX-71101060-A-C
• NM_005938.4:c.830A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005938.4(FOXO4):​c.830A>C​(p.Glu277Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: FOXO4 NM_005938.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 4.88

Genes affected

FOXO4 (HGNC:7139): (forkhead box O4) This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO4	NM_005938.4	c.830A>C	p.Glu277Ala	missense_variant	Exon 2 of 3	ENST00000374259.8	NP_005929.2
FOXO4	NM_001170931.2	c.665A>C	p.Glu222Ala	missense_variant	Exon 3 of 4		NP_001164402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO4	ENST00000374259.8	c.830A>C	p.Glu277Ala	missense_variant	Exon 2 of 3	1	NM_005938.4	ENSP00000363377.3
FOXO4	ENST00000341558.3	c.665A>C	p.Glu222Ala	missense_variant	Exon 3 of 4	5		ENSP00000342209.3
FOXO4	ENST00000464598.1	n.*217A>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual disability Uncertain:1

-

Medical Genetic Institute of Henan Province, Henan Provincial People’s Hospital

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: case-control

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Pathogenic	0.82	D;.
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T;T
M_CAP	Pathogenic	0.37	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Pathogenic	0.87	D
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.5	D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.023	D;T
Sift4G	Benign	0.086	T;D
Polyphen		1.0	D;D
Vest4		0.25
MutPred		0.18		Gain of MoRF binding (P = 0.1159);.;
MVP		0.95
MPC		0.99
ClinPred		0.93	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.39
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-70320910;