2-9484500-G-A

Variant names:

• chr2-9484500-G-A
• NM_001039613.3:c.514G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001039613.3(IAH1):​c.514G>A​(p.Asp172Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign 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. D172G) 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: 3.53
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24270263).

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.514G>A	p.Asp172Asn	missense	Exon 5 of 6	NP_001034702.1	Q2TAA2-1
	IAH1	NM_001320858.2		c.439G>A	p.Asp147Asn	missense	Exon 5 of 6	NP_001307787.1
	IAH1	NM_001320859.2		c.175G>A	p.Asp59Asn	missense	Exon 4 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.514G>A	p.Asp172Asn	missense	Exon 5 of 6	ENSP00000417580.1	Q2TAA2-1
	IAH1	ENST00000470914.5	TSL:1	c.175G>A	p.Asp59Asn	missense	Exon 4 of 5	ENSP00000419224.1	Q2TAA2-2
	IAH1	ENST00000492223.5	TSL:1	n.*306G>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000419368.1	F8WF34

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.083
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Benign	-0.058
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.065
Sift	Benign	0.076	T
Sift4G	Benign	0.089	T
Polyphen		0.0050	B
Vest4		0.23
MutPred		0.51		Loss of catalytic residue at D172 (P = 0.1374)
MVP		0.61
MPC		0.18
ClinPred		0.79	D
GERP RS		4.0
Varity_R		0.14
gMVP		0.50
Mutation Taster		=93/7	polymorphism

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: chr2-9624629;