dbSNP rs769912149: FOXD3:p.Gly276Ser (chr1-63323884-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_012183.3(FOXD3):c.826G>A(p.Gly276Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000776 in 1,289,274 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G276R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

FOXD3
NM_012183.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.97

Variant links:

Genes affected

FOXD3 (HGNC:3804): (forkhead box D3) This gene belongs to the forkhead family of transcription factors which is characterized by a distinct forkhead domain. Mutations in this gene cause autoimmune susceptibility 1. [provided by RefSeq, Nov 2008]

FOXD3 links:

FOXD3-AS1 (HGNC:40241): (FOXD3 antisense RNA 1)

FOXD3-AS1 links:

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ACMG classification

Classification made for transcript

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
FOXD3	NM_012183.3 link	c.826G>A	p.Gly276Ser	missense_variant	Exon 1 of 1	ENST00000371116.4	NP_036315.1	Q9UJU5
FOXD3-AS1	NR_121637.1 link	n.87+471C>T		intron_variant	Intron 1 of 2
FOXD3-AS1	NR_121636.1 link	n.-209C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FOXD3	ENST00000371116.4 link	c.826G>A	p.Gly276Ser	missense_variant	Exon 1 of 1	6	NM_012183.3	ENSP00000360157.2	Q9UJU5
FOXD3-AS1	ENST00000427268.1 link	n.87+471C>T		intron_variant	Intron 1 of 2	1
FOXD3-AS1	ENST00000431294.7 link	n.-108C>T		upstream_gene_variant		1
FOXD3-AS1	ENST00000697579.1 link	n.-209C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.76e-7

AC:

AN:

1289274

Hom.:

Cov.:

AF XY:

0.00000158

AC XY:

AN XY:

633564

show subpopulations

Gnomad4 AFR exome

AF:

0.0000400

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.76

Eigen

Benign

0.14

Eigen_PC

Benign

0.065

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.49

MetaRNN

Uncertain

0.54

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

0.97

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.5

REVEL

Uncertain

0.46

Sift

Benign

0.051

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.27

MutPred

0.31

Gain of glycosylation at G276 (P = 0.0011);

MVP

0.79

ClinPred

0.90

GERP RS

2.4

Varity_R

0.34

gMVP

0.78

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over