chr7-45921113-C-T

Variant names:

• chr7-45921113-C-T
• NM_000598.5:c.28G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000598.5(IGFBP3):​c.28G>A​(p.Ala10Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000745 in 1,342,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: IGFBP3 NM_000598.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.90

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17129853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IGFBP3	NM_000598.5	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 5	ENST00000613132.5	NP_000589.2
IGFBP3	NM_001013398.2	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 5		NP_001013416.1
IGFBP3	XM_047420325.1	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 4		XP_047276281.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IGFBP3	ENST00000613132.5	c.28G>A	p.Ala10Thr	missense_variant	Exon 1 of 5	5	NM_000598.5	ENSP00000477772.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.45e-7 AC: 1 AN: 1342590 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 662216

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: 9.43e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.056	T;T;.;T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.36	T;T;T;T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	.;L;L;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-0.44	.;N;N;.
REVEL	Benign	0.030
Sift	Benign	0.12	.;T;T;.
Sift4G	Uncertain	0.021	D;T;T;T
Polyphen		0.0010	.;B;.;.
Vest4		0.24
MutPred		0.32		Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);Gain of loop (P = 0.0045);
MVP		0.34
MPC		0.33
ClinPred		0.28	T
GERP RS		3.0
Varity_R		0.023
gMVP		0.59

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: chr7-45960712;