2-9478353-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong

The NM_001039613.3(IAH1):ā€‹c.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

Scores

8
6
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.90
Variant links:
Genes affected
IAH1 (HGNC:27696): (isoamyl acetate hydrolyzing esterase 1 (putative)) Enables identical protein binding activity. Predicted to be involved in lipid catabolic process. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

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
IAH1NM_001039613.3 linkc.266A>G p.Asn89Ser missense_variant 3/6 ENST00000497473.6 NP_001034702.1 Q2TAA2-1A0A140VJL6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IAH1ENST00000497473.6 linkc.266A>G p.Asn89Ser missense_variant 3/61 NM_001039613.3 ENSP00000417580.1 Q2TAA2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000407
AC:
1
AN:
245712
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133282
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000891
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000824
AC:
12
AN:
1455632
Hom.:
0
Cov.:
30
AF XY:
0.00000829
AC XY:
6
AN XY:
723454
show subpopulations
Gnomad4 AFR exome
AF:
0.0000301
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:
0.00000992
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
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 submitterclinical testingAmbry GeneticsNov 24, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Uncertain
0.063
T
BayesDel_noAF
Benign
-0.15
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
D;T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.71
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D
M_CAP
Benign
0.069
D
MetaRNN
Pathogenic
0.96
D;D
MetaSVM
Uncertain
-0.074
T
MutationAssessor
Pathogenic
3.9
H;.
PrimateAI
Benign
0.41
T
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Uncertain
0.56
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.74
MutPred
0.89
Gain of disorder (P = 0.0733);.;
MVP
0.83
MPC
0.40
ClinPred
1.0
D
GERP RS
3.8
Varity_R
0.72
gMVP
0.97

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1437846787; hg19: chr2-9618482; API