Variant chr7-23343774-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006547.3(IGF2BP3):c.1021G>A(p.Glu341Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,612,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

IGF2BP3
NM_006547.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.04

Variant links:

Genes affected

IGF2BP3 (HGNC:28868): (insulin like growth factor 2 mRNA binding protein 3) The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. A pseudogene exists on chromosome 7, and there are putative pseudogenes on other chromosomes. [provided by RefSeq, Jul 2008]

IGF2BP3 links:

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ACMG classification

Classification made for transcript

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=0.21502438).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP3	NM_006547.3 linkuse as main transcript	c.1021G>A	p.Glu341Lys	missense_variant	9/15	ENST00000258729.8	NP_006538.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IGF2BP3	ENST00000258729.8 linkuse as main transcript	c.1021G>A	p.Glu341Lys	missense_variant	9/15	1	NM_006547.3	ENSP00000258729	P1	O00425-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460754

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726714

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 10, 2022

The c.1021G>A (p.E341K) alteration is located in exon 9 (coding exon 9) of the IGF2BP3 gene. This alteration results from a G to A substitution at nucleotide position 1021, causing the glutamic acid (E) at amino acid position 341 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.93

DEOGEN2

Benign

0.040

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.033

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.012

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.030

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-0.96

REVEL

Benign

0.12

Sift

Benign

0.86

Sift4G

Benign

0.90

Polyphen

0.030

Vest4

0.50

MutPred

0.53

Loss of ubiquitination at K345 (P = 0.0368);

MVP

0.49

MPC

0.98

ClinPred

0.87

GERP RS

4.8

Varity_R

0.35

gMVP

0.86

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over