rs1647049719

Variant names:

• chr1-63323849-C-A
• NM_012183.3:c.791C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-63323849-C-A
• chr1-63323849-C-G
• chr1-63323849-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_012183.3(FOXD3):​c.791C>A​(p.Ala264Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000776 in 1,288,792 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A264G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: FOXD3 NM_012183.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXD3	NM_012183.3	c.791C>A	p.Ala264Glu	missense_variant	Exon 1 of 1	ENST00000371116.4	NP_036315.1
FOXD3-AS1	NR_121637.1	n.87+506G>T		intron_variant	Intron 1 of 2
FOXD3-AS1	NR_121636.1	n.-174G>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXD3	ENST00000371116.4	c.791C>A	p.Ala264Glu	missense_variant	Exon 1 of 1	6	NM_012183.3	ENSP00000360157.2
FOXD3-AS1	ENST00000427268.1	n.87+506G>T		intron_variant	Intron 1 of 2	1
FOXD3-AS1	ENST00000431294.7	n.-73G>T		upstream_gene_variant		1
FOXD3-AS1	ENST00000697579.1	n.-174G>T		upstream_gene_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.76e-7 AC: 1 AN: 1288792 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 640764

Gnomad4 AFR exome AF: 0.00

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: 0.00

Gnomad4 NFE exome AF: 9.85e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.0052
Eigen_PC	Benign	-0.028
FATHMM_MKL	Benign	0.65	D
LIST_S2	Benign	0.44	T
M_CAP	Pathogenic	0.62	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.091	T
MutationAssessor	Benign	0.90	L
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.35
Sift	Benign	0.086	T
Sift4G	Benign	0.13	T
Polyphen		0.99	D
Vest4		0.28
MutPred		0.45		Loss of helix (P = 0.0376);
MVP		0.73
ClinPred		0.47	T
GERP RS		2.5
Varity_R		0.22
gMVP		0.67

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-63789520;