7-45916596-ACC-TGA

Variant names:

• chr7-45916596-ACC-TGA
• NM_000598.5:c.700_702delGGTinsTCA
• IGFBP3 p.Gly234Ser

Variant summary

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

The NM_000598.5(IGFBP3):​c.700_702delGGTinsTCA​(p.Gly234Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G234D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IGFBP3 NM_000598.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000598.5. 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
	IGFBP3	NM_000598.5	MANE Select	c.700_702delGGTinsTCA	p.Gly234Ser	missense	N/A	NP_000589.2	P17936-1
	IGFBP3	NM_001013398.2		c.718_720delGGTinsTCA	p.Gly240Ser	missense	N/A	NP_001013416.1	P17936-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IGFBP3	ENST00000613132.5	TSL:5 MANE Select	c.700_702delGGTinsTCA	p.Gly234Ser	missense	N/A	ENSP00000477772.2	P17936-1
	IGFBP3	ENST00000908406.1		c.790_792delGGTinsTCA	p.Gly264Ser	missense	N/A	ENSP00000578465.1
	IGFBP3	ENST00000381083.9	TSL:5	c.718_720delGGTinsTCA	p.Gly240Ser	missense	N/A	ENSP00000370473.4	P17936-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

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.

Other links and lift over

hg19: chr7-45956195;