chr1-63323884-G-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_012183.3(FOXD3):c.826G>C(p.Gly276Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000104 in 1,440,300 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

FOXD3
NM_012183.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.97

Publications

0 publications found

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:

ENSG00000293613 (HGNC:):

ENSG00000293613 links:

ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ITGB3BP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.083937764).

BS2

High AC in GnomAdExome4 at 13 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012183.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXD3	NM_012183.3	MANE Select	c.826G>C	p.Gly276Arg	missense	Exon 1 of 1	NP_036315.1	Q9UJU5
FOXD3-AS1	NR_121637.1		n.87+471C>G		intron	N/A
FOXD3-AS1	NR_121636.1		n.-209C>G		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FOXD3	ENST00000371116.4	TSL:6 MANE Select	c.826G>C	p.Gly276Arg	missense	Exon 1 of 1	ENSP00000360157.2	Q9UJU5
FOXD3-AS1	ENST00000427268.2	TSL:1	n.196+471C>G		intron	N/A
ENSG00000293613	ENST00000715889.1		n.38+825C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000397

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000125

AC:

AN:

56104

AF XY:

0.0000909

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00300

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000101

AC:

AN:

1289274

Hom.:

Cov.:

AF XY:

0.00000631

AC XY:

AN XY:

633564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24984

American (AMR)

AF:

0.00

AC:

AN:

14032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19482

East Asian (EAS)

AF:

0.000403

AC:

AN:

29768

South Asian (SAS)

AF:

0.00

AC:

AN:

62764

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3608

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1038514

Other (OTH)

AF:

0.0000189

AC:

AN:

52776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151026

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41230

American (AMR)

AF:

0.00

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.000397

AC:

AN:

5042

South Asian (SAS)

AF:

0.00

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10306

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67702

Other (OTH)

AF:

0.00

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000434

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.94

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Uncertain

0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.78

Eigen

Benign

0.19

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.39

MetaRNN

Benign

0.084

MetaSVM

Uncertain

0.34

MutationAssessor

Benign

0.97

PhyloP100

4.0

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-3.2

REVEL

Uncertain

0.57

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.24

MutPred

0.36

Gain of methylation at G276 (P = 0.0193)

MVP

0.86

ClinPred

0.24

GERP RS

2.4

Varity_R

0.53

gMVP

0.84

Mutation Taster

=23/77

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over