chr1-63323862-G-A

Variant names:

• chr1-63323862-G-A
• rs758688806
• NM_012183.3:c.804G>A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_012183.3(FOXD3):​c.804G>A​(p.Ala268Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000054 in 1,555,918 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A268A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000050 (0 hom.)
• Consequence: FOXD3 NM_012183.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.72

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.
• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD3	NM_012183.3	c.804G>A	p.Ala268Ala	synonymous_variant	Exon 1 of 1	ENST00000371116.4	NP_036315.1
FOXD3-AS1	NR_121637.1	n.87+493C>T		intron_variant	Intron 1 of 2
FOXD3-AS1	NR_121636.1	n.-187C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD3	ENST00000371116.4	c.804G>A	p.Ala268Ala	synonymous_variant	Exon 1 of 1	6	NM_012183.3	ENSP00000360157.2
FOXD3-AS1	ENST00000427268.1	n.87+493C>T		intron_variant	Intron 1 of 2	1
FOXD3-AS1	ENST00000431294.7	n.-86C>T		upstream_gene_variant		1
FOXD3-AS1	ENST00000697579.1	n.-187C>T		upstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0000927 AC: 14 AN: 150994 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000194

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000739

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000307 AC: 5 AN: 163088 Hom.: 0 AF XY: 0.0000220 AC XY: 2 AN XY: 91094

Gnomad AFR exome AF: 0.000114

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000575

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000498 AC: 70 AN: 1404924 Hom.: 0 Cov.: 33 AF XY: 0.0000445 AC XY: 31 AN XY: 696394

Gnomad4 AFR exome AF: 0.000193

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000209

Gnomad4 NFE exome AF: 0.0000560

Gnomad4 OTH exome AF: 0.0000346

GnomAD4 genome AF: 0.0000927 AC: 14 AN: 150994 Hom.: 0 Cov.: 33 AF XY: 0.0000407 AC XY: 3 AN XY: 73700

Gnomad4 AFR AF: 0.000194

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000739

Gnomad4 OTH AF: 0.00

Bravo AF: 0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.93

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: rs758688806; hg19: chr1-63789533;