chr1-63323344-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_012183.3(FOXD3):c.286G>T(p.Val96Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,344,330 control chromosomes in the GnomAD database, including 863 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.027 ( 133 hom., cov: 33)

Exomes 𝑓: 0.016 ( 730 hom. )

Consequence

FOXD3
NM_012183.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.549

Publications

3 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001522392).

BP6

Variant 1-63323344-G-T is Benign according to our data. Variant chr1-63323344-G-T is described in ClinVar as [Benign]. Clinvar id is 3037447.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD3	NM_012183.3 link	c.286G>T	p.Val96Leu	missense_variant	Exon 1 of 1	ENST00000371116.4	NP_036315.1	Q9UJU5
FOXD3-AS1	NR_121636.1 link	n.185+147C>A		intron_variant	Intron 1 of 2
FOXD3-AS1	NR_121637.1 link	n.87+1011C>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD3	ENST00000371116.4 link	c.286G>T	p.Val96Leu	missense_variant	Exon 1 of 1	6	NM_012183.3	ENSP00000360157.2		Q9UJU5

Frequencies

GnomAD3 genomes

AF:

0.0271

AC:

4117

AN:

151872

Hom.:

133

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0491

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0916

Gnomad SAS

AF:

0.139

Gnomad FIN

AF:

0.00466

Gnomad MID

AF:

0.0256

Gnomad NFE

AF:

0.00923

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00815

AC:

108

AN:

13248

AF XY:

0.0109

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.0167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.00312

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.0200

GnomAD4 exome

AF:

0.0155

AC:

18486

AN:

1192350

Hom.:

730

Cov.:

AF XY:

0.0176

AC XY:

10133

AN XY:

576102

show subpopulations

African (AFR)

AF:

0.0497

AC:

1163

AN:

23412

American (AMR)

AF:

0.0136

AC:

120

AN:

8832

Ashkenazi Jewish (ASJ)

AF:

0.00256

AC:

AN:

16024

East Asian (EAS)

AF:

0.101

AC:

2739

AN:

27092

South Asian (SAS)

AF:

0.132

AC:

5716

AN:

43192

European-Finnish (FIN)

AF:

0.00460

AC:

185

AN:

40246

Middle Eastern (MID)

AF:

0.0213

AC:

AN:

3334

European-Non Finnish (NFE)

AF:

0.00739

AC:

7252

AN:

981858

Other (OTH)

AF:

0.0248

AC:

1199

AN:

48360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

1025

2050

3075

4100

5125

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0271

AC:

4118

AN:

151980

Hom.:

133

Cov.:

AF XY:

0.0287

AC XY:

2132

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.0491

AC:

2038

AN:

41524

American (AMR)

AF:

0.0143

AC:

218

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.0915

AC:

469

AN:

5128

South Asian (SAS)

AF:

0.139

AC:

669

AN:

4826

European-Finnish (FIN)

AF:

0.00466

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.0241

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00923

AC:

627

AN:

67940

Other (OTH)

AF:

0.0161

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

194

388

581

775

969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0254

ESP6500AA

AF:

0.0284

AC:

ESP6500EA

AF:

0.00417

AC:

ExAC

AF:

0.0162

AC:

310

Asia WGS

AF:

0.129

AC:

450

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FOXD3-related disorder

Benign:1

Dec 05, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.9

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.26

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

0.55

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.10

REVEL

Benign

0.14

Sift

Benign

0.57

Sift4G

Benign

0.32

Polyphen

0.0020

Vest4

0.014

MutPred

0.16

Loss of catalytic residue at G97 (P = 0.3108);

ClinPred

0.00024

GERP RS

0.84

Varity_R

0.087

gMVP

0.18

Mutation Taster

=96/4

polymorphism (auto)

(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

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chr1-63323344-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over