rs1033149441
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBP6
The NM_006147.4(IRF6):c.490C>G(p.Pro164Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
IRF6
NM_006147.4 missense
NM_006147.4 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 3.21
Genes affected
IRF6 (HGNC:6121): (interferon regulatory factor 6) This gene encodes a member of the interferon regulatory transcription factor (IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix DNA-binding domain and a less conserved C-terminal protein-binding domain. The encoded protein may be a transcriptional activator. Mutations in this gene can cause van der Woude syndrome and popliteal pterygium syndrome. Mutations in this gene are also associated with non-syndromic orofacial cleft type 6. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, IRF6
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21948692).
BP6
?
Variant 1-209795308-G-C is Benign according to our data. Variant chr1-209795308-G-C is described in ClinVar as [Benign]. Clinvar id is 559491.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IRF6 | NM_006147.4 | c.490C>G | p.Pro164Ala | missense_variant | 5/9 | ENST00000367021.8 | |
IRF6 | NM_001206696.2 | c.205C>G | p.Pro69Ala | missense_variant | 3/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IRF6 | ENST00000367021.8 | c.490C>G | p.Pro164Ala | missense_variant | 5/9 | 1 | NM_006147.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Orofacial cleft 10 Benign:1
Benign, no assertion criteria provided | case-control | Pharmacology and Genetics Laboratory, Bauru School of Dentistry, University of Sao Paulo | - | In silico analysis revealed polyphen prediction benign with polyphen score 0.002. Provean protein Batch - SIFT was predicted as tolerated with score 0.62. Mutation tester predicted disease causing. This rare variation was found just in a patient witn cleft and was not found in Brazillian control population without craniofacial anomalies. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;T;T
Sift4G
Benign
T;T;.
Polyphen
0.0010
.;B;.
Vest4
MutPred
0.40
.;Gain of catalytic residue at P164 (P = 0.0377);Gain of catalytic residue at P164 (P = 0.0377);
MVP
MPC
0.030
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at