rs1386064203

Variant names:

• chrX-71100790-G-A
• rs1386064203
• NM_005938.4:c.560G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-71100790-G-A
• chrX-71100790-G-C

Variant summary

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

The NM_005938.4(FOXO4):​c.560G>A​(p.Ser187Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. S187T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 22)
• Consequence: FOXO4 NM_005938.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.32
• Publications: 0 publications found

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

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=0.1536341).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO4	NM_005938.4	c.560G>A	p.Ser187Asn	missense_variant	Exon 2 of 3	ENST00000374259.8	NP_005929.2
FOXO4	NM_001170931.2	c.395G>A	p.Ser132Asn	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.560G>A	p.Ser187Asn	missense_variant	Exon 2 of 3	1	NM_005938.4	ENSP00000363377.3
FOXO4	ENST00000341558.4	c.395G>A	p.Ser132Asn	missense_variant	Exon 3 of 4	5		ENSP00000342209.3
FOXO4	ENST00000464598.1	n.253G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
FOXO4	ENST00000466874.1	n.*18G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.46	T;.
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.15	T;T
MetaSVM	Uncertain	0.44	D
MutationAssessor	Benign	1.0	L;.
PhyloP100		3.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-1.4	N;N
REVEL	Uncertain	0.32
Sift	Benign	0.11	T;T
Sift4G	Benign	0.36	T;T
Polyphen		0.0	B;P
Vest4		0.11
MutPred		0.55		Loss of glycosylation at S187 (P = 0.0026);.;
MVP		0.87
MPC		0.46
ClinPred		0.58	D
GERP RS		5.0
Varity_R		0.38
gMVP		0.37
Mutation Taster		=72/28	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: rs1386064203; hg19: chrX-70320640;