Variant 1-63323697-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_012183.3(FOXD3):c.639C>T(p.Asn213=) variant causes a synonymous change. The variant allele was found at a frequency of 0.003 in 1,614,078 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 16 hom. )

Consequence

FOXD3
NM_012183.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.25

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 (BayesDel_noAF=-0.23).

BP6

Variant 1-63323697-C-T is Benign according to our data. Variant chr1-63323697-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 775557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 258 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FOXD3	NM_012183.3 linkuse as main transcript	c.639C>T	p.Asn213=	synonymous_variant	1/1	ENST00000371116.4	NP_036315.1
FOXD3-AS1	NR_121637.1 linkuse as main transcript	n.87+658G>A		intron_variant, non_coding_transcript_variant
FOXD3-AS1	NR_121636.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
FOXD3	ENST00000371116.4 linkuse as main transcript	c.639C>T	p.Asn213=	synonymous_variant	1/1		NM_012183.3	ENSP00000360157	P1
FOXD3-AS1	ENST00000431294.7 linkuse as main transcript	n.80G>A		non_coding_transcript_exon_variant	1/3	1
FOXD3-AS1	ENST00000427268.1 linkuse as main transcript	n.87+658G>A		intron_variant, non_coding_transcript_variant		1
FOXD3-AS1	ENST00000697579.1 linkuse as main transcript			upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

258

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00303

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00134

AC:

336

AN:

251278

Hom.:

AF XY:

0.00138

AC XY:

187

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00313

AC:

4577

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00301

AC XY:

2190

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.000318

Gnomad4 NFE exome

AF:

0.00393

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00169

AC:

258

AN:

152316

Hom.:

Cov.:

AF XY:

0.00150

AC XY:

112

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00303

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00194

Hom.:

Bravo

AF:

0.00209

EpiCase

AF:

0.00251

EpiControl

AF:

0.00279

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 08, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2023	FOXD3: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.98

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