1-63323697-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 5.25

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

ACMG classification

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 GnomAd at 258 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00170 AC: 258 AN: 152200 Hom.: 3 Cov.: 33

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.: 0 AF XY: 0.00138 AC XY: 187 AN XY: 135832

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.: 16 Cov.: 34 AF XY: 0.00301 AC XY: 2190 AN XY: 727182

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.: 3 Cov.: 33 AF XY: 0.00150 AC XY: 112 AN XY: 74472

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.: 0

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	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	14
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

Other links and lift over

dbSNP: rs114453593; hg19: chr1-63789368;