chr5-139364603-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_016480.5(PAIP2):​c.178T>C​(p.Cys60Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PAIP2
NM_016480.5 missense

Scores

11
5
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84
Variant links:
Genes affected
PAIP2 (HGNC:17970): (poly(A) binding protein interacting protein 2) Enables translation repressor activity. Involved in negative regulation of translational initiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.834

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAIP2NM_016480.5 linkuse as main transcriptc.178T>C p.Cys60Arg missense_variant 3/4 ENST00000265192.9 NP_057564.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAIP2ENST00000265192.9 linkuse as main transcriptc.178T>C p.Cys60Arg missense_variant 3/41 NM_016480.5 ENSP00000265192 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsAug 09, 2021The c.178T>C (p.C60R) alteration is located in exon 3 (coding exon 2) of the PAIP2 gene. This alteration results from a T to C substitution at nucleotide position 178, causing the cysteine (C) at amino acid position 60 to be replaced by an arginine (R). 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
1.0
BayesDel_addAF
Pathogenic
0.44
D
BayesDel_noAF
Pathogenic
0.39
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.39
T;D;D;D
Eigen
Pathogenic
0.77
Eigen_PC
Pathogenic
0.76
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.95
D;.;.;D
M_CAP
Benign
0.018
T
MetaRNN
Pathogenic
0.83
D;D;D;D
MetaSVM
Uncertain
-0.14
T
MutationAssessor
Uncertain
2.2
.;M;M;M
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-10
D;D;D;D
REVEL
Uncertain
0.49
Sift
Pathogenic
0.0
D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D
Polyphen
0.98
.;D;D;D
Vest4
0.89
MutPred
0.48
Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);
MVP
0.37
MPC
2.1
ClinPred
1.0
D
GERP RS
5.8
RBP_binding_hub_radar
1.1
RBP_regulation_power_radar
2.8
Varity_R
0.97
gMVP
0.97

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: chr5-138700292; API