dbSNP rs1409965719: IAH1:p.Thr26Ile (chr2-9474643-C-T) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001039613.3(IAH1):c.77C>T(p.Thr26Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000714 in 1,400,288 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: 33)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

IAH1
NM_001039613.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.80

Publications

0 publications found

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]

IAH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.973

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039613.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IAH1	NM_001039613.3	MANE Select	c.77C>T	p.Thr26Ile	missense	Exon 1 of 6	NP_001034702.1	Q2TAA2-1
IAH1	NM_001320859.2		c.-210C>T		5_prime_UTR	Exon 1 of 5	NP_001307788.1	Q2TAA2-2
IAH1	NM_001320860.2		c.-178C>T		5_prime_UTR	Exon 1 of 5	NP_001307789.1	Q2TAA2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IAH1	ENST00000497473.6	TSL:1 MANE Select	c.77C>T	p.Thr26Ile	missense	Exon 1 of 6	ENSP00000417580.1	Q2TAA2-1
IAH1	ENST00000470914.5	TSL:1	c.-210C>T		5_prime_UTR	Exon 1 of 5	ENSP00000419224.1	Q2TAA2-2
IAH1	ENST00000492223.5	TSL:1	n.77C>T		non_coding_transcript_exon	Exon 1 of 5	ENSP00000419368.1	F8WF34

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.14e-7

AC:

AN:

1400288

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

695746

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28696

American (AMR)

AF:

0.00

AC:

AN:

37934

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24240

East Asian (EAS)

AF:

0.00

AC:

AN:

33472

South Asian (SAS)

AF:

0.00

AC:

AN:

80172

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47578

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5426

European-Non Finnish (NFE)

AF:

9.21e-7

AC:

AN:

1085230

Other (OTH)

AF:

0.00

AC:

AN:

57540

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.85

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.94

M_CAP

Pathogenic

0.79

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.2

PhyloP100

5.8

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.1

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

0.96

Vest4

0.92

MutPred

0.82

Gain of helix (P = 0.132)

MVP

0.47

MPC

0.67

ClinPred

1.0

GERP RS

4.2

PromoterAI

0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.60

gMVP

0.93

Mutation Taster

=50/50

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over