Genetic Variant IMP3:p.Arg72His (chr15-75639954-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_018285.4(IMP3):c.215G>A(p.Arg72His) variant causes a missense change. The variant allele was found at a frequency of 0.00000482 in 1,453,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

IMP3
NM_018285.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.87

Variant links:

Genes affected

IMP3 (HGNC:14497): (IMP U3 small nucleolar ribonucleoprotein 3) This gene encodes the human homolog of the yeast Imp3 protein. The protein localizes to the nucleoli and interacts with the U3 snoRNP complex. The protein contains an S4 domain. [provided by RefSeq, Jul 2008]

IMP3 links:

ENSG00000275454 (HGNC:):

ENSG00000275454 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.76

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IMP3	NM_018285.4 link	c.215G>A	p.Arg72His	missense_variant	Exon 1 of 1	ENST00000403490.3	NP_060755.1	Q9NV31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
IMP3	ENST00000403490.3 link	c.215G>A	p.Arg72His	missense_variant	Exon 1 of 1	6	NM_018285.4	ENSP00000385217.1	Q9NV31
IMP3	ENST00000314852.2 link	c.215G>A	p.Arg72His	missense_variant	Exon 2 of 2	2		ENSP00000326981.2	Q9NV31
ENSG00000275454	ENST00000621523.1 link	n.195C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000267

AC:

AN:

224760

Hom.:

AF XY:

0.0000161

AC XY:

AN XY:

124164

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000184

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1453344

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722452

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000161

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

ExAC

AF:

0.00000840

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.215G>A (p.R72H) alteration is located in exon 1 (coding exon 1) of the IMP3 gene. This alteration results from a G to A substitution at nucleotide position 215, causing the arginine (R) at amino acid position 72 to be replaced by a histidine (H). 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

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.033

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.53

D;D

Eigen

Pathogenic

0.87

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.83

.;T

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.76

D;D

MetaSVM

Uncertain

0.059

MutationAssessor

Pathogenic

3.2

M;M

PrimateAI

Pathogenic

0.81

PROVEAN

Pathogenic

-4.8

D;D

REVEL

Uncertain

0.58

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.28

MutPred

0.80

Loss of MoRF binding (P = 0.0191);Loss of MoRF binding (P = 0.0191);

MVP

0.82

MPC

1.6

ClinPred

0.95

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.77

gMVP

0.68

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