13-28138779-C-T

Variant summary

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

The NM_175854.8(PAN3):​c.122C>T​(p.Ala41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000874 in 1,372,504 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A41S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

PAN3
NM_175854.8 missense

Scores

2
3
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.03
Variant links:
Genes affected
PAN3 (HGNC:29991): (poly(A) specific ribonuclease subunit PAN3) Contributes to poly(A)-specific ribonuclease activity. Predicted to be involved in nuclear-transcribed mRNA poly(A) tail shortening. Predicted to act upstream of or within deadenylation-dependent decapping of nuclear-transcribed mRNA; positive regulation of cytoplasmic mRNA processing body assembly; and protein targeting. Part of PAN complex. [provided by Alliance of Genome Resources, Apr 2022]
PAN3-AS1 (HGNC:39932): (PAN3 antisense RNA 1)

Genome browser will be placed here

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=0.19176564).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PAN3NM_175854.8 linkc.122C>T p.Ala41Val missense_variant Exon 1 of 19 ENST00000380958.8 NP_787050.6 Q58A45-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PAN3ENST00000380958.8 linkc.122C>T p.Ala41Val missense_variant Exon 1 of 19 5 NM_175854.8 ENSP00000370345.3 Q58A45-1
PAN3ENST00000503791.5 linkn.274C>T non_coding_transcript_exon_variant Exon 1 of 14 2

Frequencies

GnomAD3 genomes
AF:
0.0000133
AC:
2
AN:
149972
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000490
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00000818
AC:
10
AN:
1222532
Hom.:
0
Cov.:
32
AF XY:
0.00000836
AC XY:
5
AN XY:
597786
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:
0.0000546
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000600
Gnomad4 OTH exome
AF:
0.0000201
GnomAD4 genome
AF:
0.0000133
AC:
2
AN:
149972
Hom.:
0
Cov.:
30
AF XY:
0.0000273
AC XY:
2
AN XY:
73210
show subpopulations
Gnomad4 AFR
AF:
0.0000490
Gnomad4 AMR
AF:
0.00
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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.122C>T (p.A41V) alteration is located in exon 1 (coding exon 1) of the PAN3 gene. This alteration results from a C to T substitution at nucleotide position 122, causing the alanine (A) at amino acid position 41 to be replaced by a valine (V). 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
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T
Eigen
Benign
-0.076
Eigen_PC
Benign
-0.030
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.81
T
M_CAP
Pathogenic
0.40
D
MetaRNN
Benign
0.19
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-0.070
N
REVEL
Benign
0.062
Sift
Uncertain
0.0050
D
Sift4G
Benign
0.13
T
Vest4
0.087
MutPred
0.33
Gain of sheet (P = 0.0221);
MVP
0.50
MPC
1.8
ClinPred
0.48
T
GERP RS
2.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
3.2
Varity_R
0.14
gMVP
0.12

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: rs1456753539; hg19: chr13-28712916; API