Genetic Variant IGFBP3:p.Ala32Glu (chr7-45921045-CG-TT) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is The variant received 2 classification points (ACGS-UK Somatic Oncogenicity v2025). O3_Moderate

The NM_000598.5(IGFBP3):c.95_96delCGinsAA (p.Ala32Glu) variant causes a missense change. The gene IGFBP3 is a tumor suppressor gene (CancerMine: 6 TSG, 6 oncogene citations). The gene IGFBP3 is a known oncogene (CancerMine: 6 TSG, 6 oncogene citations). Note: allele frequency estimates from gnomAD may be inaccurate for this variant type (MNP or indel longer than 3 bp) due to technology limitations. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Other variants at the same amino acid position have been reported in ClinVar (not pathogenic): p.A32V: unknown significance (ClinVar VariationId 4338024)

Frequency

Genomes: not found (cov: 33)

Consequence

IGFBP3
NM_000598.5 missense

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.359

Publications

0 publications found

Variant links:

Genes affected

IGFBP3 (HGNC:5472): (insulin like growth factor binding protein 3) This gene is a member of the insulin-like growth factor binding protein (IGFBP) family and encodes a protein with an IGFBP domain and a thyroglobulin type-I domain. The protein forms a ternary complex with insulin-like growth factor acid-labile subunit (IGFALS) and either insulin-like growth factor (IGF) I or II. In this form, it circulates in the plasma, prolonging the half-life of IGFs and altering their interaction with cell surface receptors. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

IGFBP3 links:

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new If you want to explore the variant's impact on the transcript NM_000598.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Uncertain_significance. The variant received 2 points.

Show applied only (1)

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	O3Absent or very rare in population		Absent or extremely rare in gnomAD (AC ≤ 2) — O3 moderate; GnomAD: AF = absent, AC = 0 — absent/extremely rare (O3 moderate [+2])

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000598.5. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	IGFBP3 NM_000598.5	MANE Select	c.95_96delCGinsAA p.Ala32Glu	missense	N/A	Prot: NP_000589.2 UniProt: P17936-1
	IGFBP3 NM_001013398.2		c.95_96delCGinsAA p.Ala32Glu	missense	N/A	Prot: NP_001013416.1 UniProt: P17936-2

IGFBP3 NM_000598.5

MANE Select

HGVSc / HGVSpc.95_96delCGinsAAp.Ala32Glu

Exon rankN/A

missense

Prot: NP_000589.2UniProt: P17936-1

IGFBP3 NM_001013398.2

HGVSc / HGVSpc.95_96delCGinsAAp.Ala32Glu

Exon rankN/A

missense

Prot: NP_001013416.1UniProt: P17936-2

Ensembl Transcripts

Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
IGFBP3 ENST00000613132.5	TSL:5MANE Select	c.95_96delCGinsAA p.Ala32Glu	missense	N/A	Prot: ENSP00000477772.2 UniProt: P17936-1
IGFBP3 ENST00000908406.1		c.95_96delCGinsAA p.Ala32Glu	missense	N/A	Prot: ENSP00000578465.1 UniProt: A0ACI8RUV2
IGFBP3 ENST00000381083.9	TSL:5	c.95_96delCGinsAA p.Ala32Glu	missense	N/A	Prot: ENSP00000370473.4 UniProt: P17936-2

IGFBP3 ENST00000613132.5

TSL:5MANE Select

HGVSc / HGVSpc.95_96delCGinsAAp.Ala32Glu

Exon rankN/A

missense

Prot: ENSP00000477772.2UniProt: P17936-1

IGFBP3 ENST00000908406.1

HGVSc / HGVSpc.95_96delCGinsAAp.Ala32Glu

Exon rankN/A

missense

Prot: ENSP00000578465.1UniProt: A0ACI8RUV2

IGFBP3 ENST00000381083.9

TSL:5

HGVSc / HGVSpc.95_96delCGinsAAp.Ala32Glu

Exon rankN/A

missense

Prot: ENSP00000370473.4UniProt: P17936-2

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 2 sources Large-scale international reference populations
GnomAD3 genomes	AF:	AC:	Hom:	AN:	Cov:33
GnomAD4 genome	AF:	AC:	Hom:	AN:	Cov:33

Showing 2 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
PhyloP100	Benign	0.36

Showing 1 of 1 scores

Splicing Scores

No splicing scores have been computed for this variant.

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACGS-UK Somatic Oncogenicity v2025

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational Scores

Splicing Scores

MaveDB functional evidence ?

Publications

Other links and lift over

MaveDB functional evidence