rs201230473

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_014976.2(PDCD11):​c.1241G>A​(p.Gly414Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000197 in 1,613,410 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

PDCD11
NM_014976.2 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.89

Publications

5 publications found
Variant links:
Genes affected
PDCD11 (HGNC:13408): (programmed cell death 11) PDCD11 is a NF-kappa-B (NFKB1; 164011)-binding protein that colocalizes with U3 RNA (MIM 180710) in the nucleolus and is required for rRNA maturation and generation of 18S rRNA (Sweet et al., 2003 [PubMed 14624448]; Sweet et al., 2008 [PubMed 17654514]).[supplied by OMIM, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2
High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PDCD11NM_014976.2 linkc.1241G>A p.Gly414Glu missense_variant Exon 10 of 36 ENST00000369797.8 NP_055791.1 Q14690

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PDCD11ENST00000369797.8 linkc.1241G>A p.Gly414Glu missense_variant Exon 10 of 36 1 NM_014976.2 ENSP00000358812.3 Q14690
PDCD11ENST00000649849.1 linkc.1241G>A p.Gly414Glu missense_variant Exon 10 of 36 ENSP00000498205.1 A0A3B3IUD7

Frequencies

GnomAD3 genomes
AF:
0.000171
AC:
26
AN:
152122
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000943
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000323
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.000243
AC:
61
AN:
251016
AF XY:
0.000287
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.000232
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000396
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000200
AC:
292
AN:
1461288
Hom.:
0
Cov.:
31
AF XY:
0.000220
AC XY:
160
AN XY:
726992
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33458
American (AMR)
AF:
0.000202
AC:
9
AN:
44658
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39696
South Asian (SAS)
AF:
0.000151
AC:
13
AN:
86232
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53250
Middle Eastern (MID)
AF:
0.000347
AC:
2
AN:
5768
European-Non Finnish (NFE)
AF:
0.000231
AC:
257
AN:
1111714
Other (OTH)
AF:
0.000166
AC:
10
AN:
60382
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.487
Heterozygous variant carriers
0
17
34
50
67
84
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.000171
AC:
26
AN:
152122
Hom.:
0
Cov.:
32
AF XY:
0.000161
AC XY:
12
AN XY:
74306
show subpopulations
African (AFR)
AF:
0.0000241
AC:
1
AN:
41412
American (AMR)
AF:
0.0000655
AC:
1
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5192
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.0000943
AC:
1
AN:
10606
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.000323
AC:
22
AN:
68030
Other (OTH)
AF:
0.000478
AC:
1
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.523
Heterozygous variant carriers
0
2
4
6
8
10
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.000351
Hom.:
0
Bravo
AF:
0.000227
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000778
AC:
3
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.000288
AC:
35
EpiCase
AF:
0.000491
EpiControl
AF:
0.000948

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 12, 2025
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.1241G>A (p.G414E) alteration is located in exon 10 (coding exon 9) of the PDCD11 gene. This alteration results from a G to A substitution at nucleotide position 1241, causing the glycine (G) at amino acid position 414 to be replaced by a glutamic acid (E). 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
0.21
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.11
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
.;T
Eigen
Pathogenic
0.82
Eigen_PC
Pathogenic
0.79
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.83
T;T
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Benign
-0.58
T
MutationAssessor
Uncertain
2.7
.;M
PhyloP100
6.9
PrimateAI
Uncertain
0.56
T
PROVEAN
Pathogenic
-5.9
.;D
REVEL
Uncertain
0.42
Sift
Uncertain
0.011
.;D
Sift4G
Uncertain
0.044
.;D
Polyphen
1.0
.;D
Vest4
0.64
MVP
0.68
MPC
0.86
ClinPred
0.84
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.53
gMVP
0.65
Mutation Taster
=71/29
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs201230473; hg19: chr10-105173778; COSMIC: COSV63935205; API