2-9478353-A-G
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001039613.3(IAH1):āc.266A>Gā(p.Asn89Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000824 in 1,455,632 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0000082 ( 0 hom. )
Consequence
IAH1
NM_001039613.3 missense
NM_001039613.3 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 6.90
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
In a site Transition state stabilizer (size 0) in uniprot entity IAH1_HUMAN
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
IAH1 | NM_001039613.3 | c.266A>G | p.Asn89Ser | missense_variant | 3/6 | ENST00000497473.6 | NP_001034702.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000407 AC: 1AN: 245712Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133282
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GnomAD4 exome AF: 0.00000824 AC: 12AN: 1455632Hom.: 0 Cov.: 30 AF XY: 0.00000829 AC XY: 6AN XY: 723454
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GnomAD4 genome Cov.: 32
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32
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 | Nov 24, 2024 | The c.266A>G (p.N89S) alteration is located in exon 3 (coding exon 3) of the IAH1 gene. This alteration results from a A to G substitution at nucleotide position 266, causing the asparagine (N) at amino acid position 89 to be replaced by a serine (S). 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
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;.
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Gain of disorder (P = 0.0733);.;
MVP
MPC
ClinPred
D
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