Variant chr7-23312812-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006547.3(IGF2BP3):c.1564G>A(p.Val522Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000768 in 1,612,368 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 2 hom. )

Consequence

IGF2BP3
NM_006547.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.12

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.022533685).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IGF2BP3	NM_006547.3 linkuse as main transcript	c.1564G>A	p.Val522Ile	missense_variant	14/15	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.1564G>A	p.Val522Ile	missense_variant	14/15	1	NM_006547.3	ENSP00000258729	P1	O00425-1
IGF2BP3	ENST00000619562.4 linkuse as main transcript	c.421G>A	p.Val141Ile	missense_variant	7/8	1		ENSP00000480267		O00425-2
IGF2BP3	ENST00000498363.1 linkuse as main transcript	n.364G>A		non_coding_transcript_exon_variant	3/4	2
IGF2BP3	ENST00000421467.6 linkuse as main transcript	c.*1100G>A		3_prime_UTR_variant, NMD_transcript_variant	11/12	5		ENSP00000395936

Frequencies

GnomAD3 genomes

AF:

0.000572

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000693

AC:

173

AN:

249542

Hom.:

AF XY:

0.000623

AC XY:

AN XY:

134864

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000559

Gnomad ASJ exome

AF:

0.00359

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000231

Gnomad NFE exome

AF:

0.000936

Gnomad OTH exome

AF:

0.000819

GnomAD4 exome

AF:

0.000789

AC:

1152

AN:

1460030

Hom.:

Cov.:

AF XY:

0.000723

AC XY:

525

AN XY:

726300

show subpopulations

Gnomad4 AFR exome

AF:

0.000210

Gnomad4 AMR exome

AF:

0.000543

Gnomad4 ASJ exome

AF:

0.00322

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000169

Gnomad4 NFE exome

AF:

0.000848

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.000571

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000631

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000292

Hom.:

Bravo

AF:

0.000684

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.000642

AC:

EpiCase

AF:

0.000872

EpiControl

AF:

0.000949

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

Jul 14, 2021

The c.1564G>A (p.V522I) alteration is located in exon 14 (coding exon 14) of the IGF2BP3 gene. This alteration results from a G to A substitution at nucleotide position 1564, causing the valine (V) at amino acid position 522 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.031

T;.

Eigen

Benign

0.029

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.0051

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.22

N;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.35

N;.

REVEL

Benign

0.12

Sift

Benign

0.57

T;.

Sift4G

Benign

0.23

T;T

Polyphen

0.025

B;.

Vest4

0.56

MVP

0.33

MPC

0.67

ClinPred

0.017

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.086

gMVP

0.28

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