NM_018285.4:c.167G>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_018285.4(IMP3):​c.167G>C​(p.Arg56Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000524 in 1,601,568 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

IMP3
NM_018285.4 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 39 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
IMP3NM_018285.4 linkc.167G>C p.Arg56Pro missense_variant Exon 1 of 1 ENST00000403490.3 NP_060755.1 Q9NV31

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
IMP3ENST00000403490.3 linkc.167G>C p.Arg56Pro missense_variant Exon 1 of 1 6 NM_018285.4 ENSP00000385217.1 Q9NV31
IMP3ENST00000314852.2 linkc.167G>C p.Arg56Pro missense_variant Exon 2 of 2 2 ENSP00000326981.2 Q9NV31
ENSG00000275454ENST00000621523.1 linkn.243C>G non_coding_transcript_exon_variant Exon 1 of 1 6

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152256
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000916
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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
GnomAD3 exomes
AF:
0.0000776
AC:
17
AN:
219060
Hom.:
0
AF XY:
0.0000330
AC XY:
4
AN XY:
121294
show subpopulations
Gnomad AFR exome
AF:
0.00134
Gnomad AMR exome
AF:
0.00
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:
0.0000310
AC:
45
AN:
1449312
Hom.:
0
Cov.:
32
AF XY:
0.0000194
AC XY:
14
AN XY:
720160
show subpopulations
Gnomad4 AFR exome
AF:
0.00124
Gnomad4 AMR exome
AF:
0.0000232
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:
0.0000501
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152256
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74386
show subpopulations
Gnomad4 AFR
AF:
0.000916
Gnomad4 AMR
AF:
0.0000654
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
Alfa
AF:
0.000142
Hom.:
0
Bravo
AF:
0.000351
ExAC
AF:
0.0000837
AC:
10

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.167G>C (p.R56P) alteration is located in exon 1 (coding exon 1) of the IMP3 gene. This alteration results from a G to C substitution at nucleotide position 167, causing the arginine (R) at amino acid position 56 to be replaced by a proline (P). 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
0.96
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Uncertain
0.11
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.36
T;T
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.93
.;D
M_CAP
Pathogenic
0.60
D
MetaRNN
Uncertain
0.63
D;D
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Pathogenic
3.1
M;M
PrimateAI
Pathogenic
0.90
D
PROVEAN
Pathogenic
-5.6
D;D
REVEL
Uncertain
0.34
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.020
D;D
Polyphen
1.0
D;D
Vest4
0.74
MutPred
0.66
Loss of MoRF binding (P = 0.0202);Loss of MoRF binding (P = 0.0202);
MVP
0.80
MPC
1.7
ClinPred
0.45
T
GERP RS
6.1
Varity_R
0.89
gMVP
0.88

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.

Other links and lift over

dbSNP: rs746369854; hg19: chr15-75932343; API