chr2-9481300-C-G

Variant names:

• chr2-9481300-C-G
• NM_001039613.3:c.298C>G

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001039613.3(IAH1):​c.298C>G​(p.Gln100Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q100H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IAH1 NM_001039613.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.793

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IAH1	NM_001039613.3	MANE Select	c.298C>G	p.Gln100Glu	missense	Exon 4 of 6	NP_001034702.1	Q2TAA2-1
	IAH1	NM_001320858.2		c.223C>G	p.Gln75Glu	missense	Exon 4 of 6	NP_001307787.1
	IAH1	NM_001320859.2		c.-42C>G		5_prime_UTR	Exon 3 of 5	NP_001307788.1	Q2TAA2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IAH1	ENST00000497473.6	TSL:1 MANE Select	c.298C>G	p.Gln100Glu	missense	Exon 4 of 6	ENSP00000417580.1	Q2TAA2-1
	IAH1	ENST00000470914.5	TSL:1	c.-42C>G		5_prime_UTR	Exon 3 of 5	ENSP00000419224.1	Q2TAA2-2
	IAH1	ENST00000492223.5	TSL:1	n.*90C>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000419368.1	F8WF34

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.79	D
MetaSVM	Uncertain	0.52	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		7.6
PrimateAI	Benign	0.48	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.99	D
Vest4		0.81
MutPred		0.76		Gain of disorder (P = 0.0598)
MVP		0.72
MPC		0.68
ClinPred		0.99	D
GERP RS		5.8
Varity_R		0.57
gMVP		0.95
Mutation Taster		=150/150

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

Other links and lift over

hg19: chr2-9621429;