rs573596066

Variant names:

• chr1-41382511-C-G
• rs573596066
• ENST00000641094.2:c.1309C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-41382511-C-G
• chr1-41382511-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000641094.2(FOXO6):​c.1309C>G​(p.Leu437Val) 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. Synonymous variant affecting the same amino acid position (i.e. L437L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FOXO6 ENST00000641094.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 0 publications found

Genes affected

FOXO6 (HGNC:24814): (forkhead box O6) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in positive regulation of dendritic spine development and regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42032626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO6	NM_001291281.3	c.1309C>G	p.Leu437Val	missense_variant	Exon 3 of 3		NP_001278210.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO6	ENST00000641094.2	c.1309C>G	p.Leu437Val	missense_variant	Exon 3 of 3			ENSP00000493184.1
FOXO6	ENST00000686812.1	c.925C>G	p.Leu309Val	missense_variant	Exon 3 of 3			ENSP00000509631.1
FOXO6	ENST00000372591.1	n.1319C>G		non_coding_transcript_exon_variant	Exon 2 of 2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.76
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	-0.051
Eigen_PC	Benign	-0.072
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.85	D
MetaRNN	Benign	0.42	T
PhyloP100		0.21
ClinPred		0.74	D
GERP RS		3.4
Varity_R		0.11
gMVP		0.45
Mutation Taster		=88/12	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: rs573596066; hg19: chr1-41848183;