1-63323344-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

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 criteria provided, single submitter B:1

Conservation

PhyloP100: 0.549

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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/exons	MANE
FOXD3	NM_012183.3 linkuse as main transcript	c.286G>T	p.Val96Leu	missense_variant	1/1	ENST00000371116.4
FOXD3-AS1	NR_121637.1 linkuse as main transcript	n.87+1011C>A		intron_variant, non_coding_transcript_variant
FOXD3-AS1	NR_121636.1 linkuse as main transcript	n.185+147C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FOXD3	ENST00000371116.4 linkuse as main transcript	c.286G>T	p.Val96Leu	missense_variant	1/1		NM_012183.3	P1
FOXD3-AS1	ENST00000427268.1 linkuse as main transcript	n.87+1011C>A		intron_variant, non_coding_transcript_variant		1
FOXD3-AS1	ENST00000431294.7 linkuse as main transcript	n.286+147C>A		intron_variant, non_coding_transcript_variant		1
FOXD3-AS1	ENST00000697579.1 linkuse as main transcript	n.203+129C>A		intron_variant, non_coding_transcript_variant

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

GnomAD3 exomes

AF:

0.00815

AC:

108

AN:

13248

Hom.:

AF XY:

0.0109

AC XY:

AN XY:

6694

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 SAS exome

AF:

0.157

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

Gnomad4 AFR exome

AF:

0.0497

Gnomad4 AMR exome

AF:

0.0136

Gnomad4 ASJ exome

AF:

0.00256

Gnomad4 EAS exome

AF:

0.101

Gnomad4 SAS exome

AF:

0.132

Gnomad4 FIN exome

AF:

0.00460

Gnomad4 NFE exome

AF:

0.00739

Gnomad4 OTH exome

AF:

0.0248

GnomAD4 genome

AF:

0.0271

AC:

4118

AN:

151980

Hom.:

133

Cov.:

AF XY:

0.0287

AC XY:

2132

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0491

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0915

Gnomad4 SAS

AF:

0.139

Gnomad4 FIN

AF:

0.00466

Gnomad4 NFE

AF:

0.00923

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0163

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: criteria provided, single submitter

LINK: link

Submissions by phenotype

FOXD3-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

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

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

MutationTaster

Benign

1.0

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over