chr2-9484480-C-G

Variant names:

• chr2-9484480-C-G
• NM_001039613.3:c.494C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039613.3(IAH1):​c.494C>G​(p.Ala165Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,856 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: IAH1 NM_001039613.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.74

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IAH1	NM_001039613.3	c.494C>G	p.Ala165Gly	missense_variant	Exon 5 of 6	ENST00000497473.6	NP_001034702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IAH1	ENST00000497473.6	c.494C>G	p.Ala165Gly	missense_variant	Exon 5 of 6	1	NM_001039613.3	ENSP00000417580.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461856 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727230

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T;.;T;.;T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.81	T;.;T;T;T
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.65	D;D;D;D;D
MetaSVM	Benign	-0.41	T
MutationAssessor	Pathogenic	3.7	.;.;H;.;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.1	D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.012	D;D;D;D;D
Sift4G	Uncertain	0.029	D;D;D;D;D
Polyphen		1.0	.;.;D;.;.
Vest4		0.35, 0.35
MutPred		0.72		.;.;Gain of catalytic residue at A165 (P = 0.2441);.;.;
MVP		0.18
MPC		0.36
ClinPred		0.97	D
GERP RS		2.3
Varity_R		0.38
gMVP		0.61

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-9624609;