12-6555414-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001193457.2(IFFO1):c.616G>A(p.Gly206Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000164 in 1,461,700 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
IFFO1
NM_001193457.2 missense
NM_001193457.2 missense
Scores
4
8
6
Clinical Significance
Conservation
PhyloP100: 5.53
Genes affected
IFFO1 (HGNC:24970): (intermediate filament family orphan 1) This gene is a member of the intermediate filament family. Intermediate filaments are proteins which are primordial components of the cytoskeleton and nuclear envelope. The proteins encoded by the members of this gene family are evolutionarily and structurally related but have limited sequence homology, with the exception of the central rod domain. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.769
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFFO1 | NM_001193457.2 | c.616G>A | p.Gly206Arg | missense_variant | 1/10 | ENST00000619571.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFFO1 | ENST00000619571.5 | c.616G>A | p.Gly206Arg | missense_variant | 1/10 | 2 | NM_001193457.2 | A1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249270Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135098
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GnomAD4 exome AF: 0.0000164 AC: 24AN: 1461700Hom.: 0 Cov.: 32 AF XY: 0.0000220 AC XY: 16AN XY: 727174
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GnomAD4 genome Cov.: 32
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32
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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 | Oct 05, 2022 | The c.616G>A (p.G206R) alteration is located in exon 1 (coding exon 1) of the IFFO1 gene. This alteration results from a G to A substitution at nucleotide position 616, causing the glycine (G) at amino acid position 206 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;.;D
REVEL
Uncertain
Sift
Benign
D;D;.;D
Sift4G
Uncertain
D;D;D;D
Polyphen
D;D;.;D
Vest4
MutPred
Gain of MoRF binding (P = 0.029);Gain of MoRF binding (P = 0.029);Gain of MoRF binding (P = 0.029);Gain of MoRF binding (P = 0.029);
MVP
MPC
1.6
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
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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