rs1553960

Variant summary

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

The NM_020144.5(PAPOLB):ā€‹c.1347T>Gā€‹(p.Asn449Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.000010 ( 0 hom. )

Consequence

PAPOLB
NM_020144.5 missense

Scores

2
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0500
Variant links:
Genes affected
PAPOLB (HGNC:15970): (poly(A) polymerase beta) Predicted to enable polynucleotide adenylyltransferase activity. Predicted to be involved in mRNA polyadenylation. Predicted to be located in endoplasmic reticulum. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
RADIL (HGNC:22226): (Rap associating with DIL domain) Predicted to enable GTPase binding activity. Acts upstream of or within substrate adhesion-dependent cell spreading. Located in microtubule. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

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=0.1745961).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PAPOLBNM_020144.5 linkuse as main transcriptc.1347T>G p.Asn449Lys missense_variant 1/1 ENST00000404991.2
RADILNM_018059.5 linkuse as main transcriptc.535+17141T>G intron_variant ENST00000399583.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PAPOLBENST00000404991.2 linkuse as main transcriptc.1347T>G p.Asn449Lys missense_variant 1/1 NM_020144.5 P1
RADILENST00000399583.4 linkuse as main transcriptc.535+17141T>G intron_variant 5 NM_018059.5 P1Q96JH8-4
RADILENST00000445392.5 linkuse as main transcriptc.535+17141T>G intron_variant, NMD_transcript_variant 5

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152038
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000120
AC:
3
AN:
250302
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135726
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:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461832
Hom.:
0
Cov.:
38
AF XY:
0.0000138
AC XY:
10
AN XY:
727214
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:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152038
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74264
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
16
DANN
Benign
0.96
Eigen
Benign
-0.44
Eigen_PC
Benign
-0.41
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.17
T
MetaSVM
Benign
-0.81
T
MutationTaster
Benign
0.000066
P;P;P
PrimateAI
Uncertain
0.66
T
REVEL
Benign
0.052
Sift4G
Benign
0.34
T
Polyphen
0.22
B
Vest4
0.28
MVP
0.35
MPC
0.14
ClinPred
0.23
T
GERP RS
1.5
gMVP
0.051

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: rs1553960; hg19: chr7-4900095; API