rs909124051

Variant names:

• chr6-108561287-C-G
• rs909124051
• NM_001455.4:c.79C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-108561287-C-G
• chr6-108561287-C-T

Variant summary

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

The NM_001455.4(FOXO3):​c.79C>G​(p.Arg27Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. R27C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0025 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FOXO3 NM_001455.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.59
• Publications: 0 publications found

Genes affected

FOXO3 (HGNC:3821): (forkhead box O3) This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXO3	NM_001455.4	c.79C>G	p.Arg27Gly	missense_variant	Exon 1 of 3	ENST00000406360.2	NP_001446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXO3	ENST00000406360.2	c.79C>G	p.Arg27Gly	missense_variant	Exon 1 of 3	1	NM_001455.4	ENSP00000385824.1
FOXO3	ENST00000343882.10	c.79C>G	p.Arg27Gly	missense_variant	Exon 2 of 4	1		ENSP00000339527.6

Frequencies

GnomAD3 genomes AF: 0.00247 AC: 364 AN: 147300 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00932

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000994

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00195

GnomAD2 exomes AF: 0.000232 AC: 37 AN: 159618 AF XY: 0.000171

Gnomad AFR exome AF: 0.00511

Gnomad AMR exome AF: 0.000158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000160 AC: 225 AN: 1409632 Hom.: 0 Cov.: 32 AF XY: 0.000159 AC XY: 111 AN XY: 697666

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00608 AC: 181 AN: 29764

American (AMR) AF: 0.000672 AC: 25 AN: 37190

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25226

East Asian (EAS) AF: 0.00 AC: 0 AN: 36598

South Asian (SAS) AF: 0.0000124 AC: 1 AN: 80384

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48452

Middle Eastern (MID) AF: 0.000245 AC: 1 AN: 4082

European-Non Finnish (NFE) AF: 0.00000367 AC: 4 AN: 1089732

Other (OTH) AF: 0.000223 AC: 13 AN: 58204

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00248 AC: 365 AN: 147408 Hom.: 0 Cov.: 33 AF XY: 0.00248 AC XY: 179 AN XY: 72188

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00932 AC: 345 AN: 37012

American (AMR) AF: 0.000992 AC: 15 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5142

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67956

Other (OTH) AF: 0.00193 AC: 4 AN: 2076

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00211 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Uncertain	0.98
DEOGEN2	Pathogenic	0.93	D;D
Eigen	Benign	0.017
Eigen_PC	Benign	0.0023
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Pathogenic	0.98	.;D
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Uncertain	0.72	D
MutationAssessor	Uncertain	2.2	M;M
PhyloP100		2.6
PrimateAI	Pathogenic	0.95	D
PROVEAN	Pathogenic	-5.1	D;D
REVEL	Pathogenic	0.65
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.57	P;P
Vest4		0.51
MVP		0.95
ClinPred		0.18	T
GERP RS		3.1
PromoterAI		-0.045	Neutral
Varity_R		0.89
gMVP		0.71
Mutation Taster		=58/42	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: rs909124051; hg19: chr6-108882490;