chr1-63323197-C-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_012183.3(FOXD3):c.139C>A(p.Pro47Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000907 in 1,544,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000093 ( 0 hom. )
Consequence
FOXD3
NM_012183.3 missense
NM_012183.3 missense
Scores
2
2
15
Clinical Significance
Conservation
PhyloP100: -0.0980
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.22865957).
BS2
High AC in GnomAdExome4 at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FOXD3 | NM_012183.3 | c.139C>A | p.Pro47Thr | missense_variant | 1/1 | ENST00000371116.4 | |
FOXD3-AS1 | NR_121637.1 | n.87+1158G>T | intron_variant, non_coding_transcript_variant | ||||
FOXD3-AS1 | NR_121636.1 | n.185+294G>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FOXD3 | ENST00000371116.4 | c.139C>A | p.Pro47Thr | missense_variant | 1/1 | NM_012183.3 | P1 | ||
FOXD3-AS1 | ENST00000427268.1 | n.87+1158G>T | intron_variant, non_coding_transcript_variant | 1 | |||||
FOXD3-AS1 | ENST00000431294.7 | n.286+294G>T | intron_variant, non_coding_transcript_variant | 1 | |||||
FOXD3-AS1 | ENST00000697579.1 | n.203+276G>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000142 AC: 2AN: 140926Hom.: 0 AF XY: 0.0000261 AC XY: 2AN XY: 76660
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GnomAD4 exome AF: 0.00000934 AC: 13AN: 1392180Hom.: 0 Cov.: 33 AF XY: 0.0000102 AC XY: 7AN XY: 687790
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152066Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74282
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.139C>A (p.P47T) alteration is located in exon 1 (coding exon 1) of the FOXD3 gene. This alteration results from a C to A substitution at nucleotide position 139, causing the proline (P) at amino acid position 47 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Gain of glycosylation at P47 (P = 0.0122);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at