2-9474571-C-G

Variant names:

• chr2-9474571-C-G
• NM_001039613.3:c.5C>G

Variant summary

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

The NM_001039613.3(IAH1):​c.5C>G​(p.Ala2Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,362,510 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: 0.0000015 (0 hom.)
• Consequence: IAH1 NM_001039613.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.49

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.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 6	ENST00000497473.6	NP_001034702.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IAH1	ENST00000497473.6	c.5C>G	p.Ala2Gly	missense_variant	Exon 1 of 6	1	NM_001039613.3	ENSP00000417580.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1362510 Hom.: 0 Cov.: 32 AF XY: 0.00000148 AC XY: 1 AN XY: 676670

Gnomad4 AFR exome AF: 0.0000362

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000130

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.11
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.060
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.45	T
M_CAP	Pathogenic	0.89	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.66	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.067
Sift	Benign	0.048	D
Sift4G	Benign	0.085	T
Polyphen		0.29	B
Vest4		0.34
MutPred		0.23		Gain of loop (P = 0.0435);
MVP		0.46
MPC		0.39
ClinPred		0.83	D
GERP RS		3.9
Varity_R		0.14
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: chr2-9614700;