12-56318321-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_014871.6(PAN2):​c.3478C>T​(p.His1160Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PAN2
NM_014871.6 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02
Variant links:
Genes affected
PAN2 (HGNC:20074): (poly(A) specific ribonuclease subunit PAN2) This gene encodes a deadenylase that functions as the catalytic subunit of the polyadenylate binding protein dependent poly(A) nuclease complex. The encoded protein is a magnesium dependent 3' to 5' exoribonuclease that is involved in the degradation of cytoplasmic mRNAs. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), PAN2. . Gene score misZ 3.1762 (greater than the threshold 3.09). Trascript score misZ 4.8346 (greater than threshold 3.09). GenCC has associacion of gene with multiple congenital anomalies/dysmorphic syndrome-intellectual disability.
BP4
Computational evidence support a benign effect (MetaRNN=0.22468027).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PAN2NM_014871.6 linkuse as main transcriptc.3478C>T p.His1160Tyr missense_variant 25/26 ENST00000440411.8 NP_055686.4 Q504Q3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PAN2ENST00000440411.8 linkuse as main transcriptc.3478C>T p.His1160Tyr missense_variant 25/261 NM_014871.6 ENSP00000388231.3 Q504Q3-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251492
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461848
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727226
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 GeneticsOct 29, 2021The c.3490C>T (p.H1164Y) alteration is located in exon 25 (coding exon 24) of the PAN2 gene. This alteration results from a C to T substitution at nucleotide position 3490, causing the histidine (H) at amino acid position 1164 to be replaced by a tyrosine (Y). 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
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.067
T;T;.;.;T
Eigen
Uncertain
0.29
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
.;D;D;D;.
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.22
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.34
N;N;.;.;N
PrimateAI
Uncertain
0.67
T
PROVEAN
Benign
-1.8
N;.;N;N;N
REVEL
Benign
0.11
Sift
Uncertain
0.024
D;.;D;D;D
Sift4G
Uncertain
0.021
D;D;D;D;D
Polyphen
0.40
B;B;P;P;B
Vest4
0.31
MutPred
0.36
Gain of phosphorylation at H1164 (P = 0.0376);Gain of phosphorylation at H1164 (P = 0.0376);.;.;Gain of phosphorylation at H1164 (P = 0.0376);
MVP
0.24
MPC
0.74
ClinPred
0.62
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.30
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs760115869; hg19: chr12-56712105; API