Genetic Variant NM_014976.2:c.1867G>T (chr10-103417888-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014976.2(PDCD11):c.1867G>T(p.Ala623Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0631 in 1,614,016 control chromosomes in the GnomAD database, including 3,647 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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: 𝑓 0.047 ( 221 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3426 hom. )

Consequence

PDCD11
NM_014976.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.124

Publications

22 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]

PDCD11 links:

ENSG00000301927 (HGNC:):

ENSG00000301927 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022095144).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD11	NM_014976.2 link	c.1867G>T	p.Ala623Ser	missense_variant	Exon 14 of 36	ENST00000369797.8	NP_055791.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PDCD11	ENST00000369797.8 link	c.1867G>T	p.Ala623Ser	missense_variant	Exon 14 of 36	1	NM_014976.2	ENSP00000358812.3
PDCD11	ENST00000649849.1 link	c.1867G>T	p.Ala623Ser	missense_variant	Exon 14 of 36			ENSP00000498205.1
ENSG00000301927	ENST00000782928.1 link	n.251-3C>A		splice_region_variant, intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.0466

AC:

7092

AN:

152168

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0145

Gnomad AMI

AF:

0.195

Gnomad AMR

AF:

0.0501

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0299

Gnomad FIN

AF:

0.0236

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.0690

Gnomad OTH

AF:

0.0540

GnomAD2 exomes

AF:

0.0502

AC:

12617

AN:

251430

AF XY:

0.0508

show subpopulations

Gnomad AFR exome

AF:

0.0151

Gnomad AMR exome

AF:

0.0403

Gnomad ASJ exome

AF:

0.0927

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0269

Gnomad NFE exome

AF:

0.0716

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0648

AC:

94741

AN:

1461730

Hom.:

3426

Cov.:

AF XY:

0.0639

AC XY:

46485

AN XY:

727158

show subpopulations

African (AFR)

AF:

0.0116

AC:

387

AN:

33480

American (AMR)

AF:

0.0408

AC:

1824

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.0921

AC:

2407

AN:

26132

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0297

AC:

2558

AN:

86256

European-Finnish (FIN)

AF:

0.0294

AC:

1573

AN:

53420

Middle Eastern (MID)

AF:

0.103

AC:

592

AN:

5768

European-Non Finnish (NFE)

AF:

0.0735

AC:

81694

AN:

1111866

Other (OTH)

AF:

0.0613

AC:

3703

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

4475

8949

13424

17898

22373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3048

6096

9144

12192

15240

<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:

0.0466

AC:

7091

AN:

152286

Hom.:

221

Cov.:

AF XY:

0.0443

AC XY:

3300

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0144

AC:

600

AN:

41576

American (AMR)

AF:

0.0500

AC:

765

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

324

AN:

3472

East Asian (EAS)

AF:

0.000386

AC:

AN:

5182

South Asian (SAS)

AF:

0.0305

AC:

147

AN:

4818

European-Finnish (FIN)

AF:

0.0236

AC:

250

AN:

10612

Middle Eastern (MID)

AF:

0.0782

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0690

AC:

4690

AN:

68008

Other (OTH)

AF:

0.0534

AC:

113

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

351

701

1052

1402

1753

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0641

Hom.:

1176

Bravo

AF:

0.0478

TwinsUK

AF:

0.0739

AC:

274

ALSPAC

AF:

0.0701

AC:

270

ESP6500AA

AF:

0.0179

AC:

ESP6500EA

AF:

0.0695

AC:

598

ExAC

AF:

0.0496

AC:

6027

Asia WGS

AF:

0.0150

AC:

AN:

3478

EpiCase

AF:

0.0741

EpiControl

AF:

0.0768

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.2

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.0059

.;T

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.43

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

.;N

PhyloP100

0.12

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.31

.;N

REVEL

Benign

0.035

Sift

Benign

0.76

.;T

Sift4G

Benign

0.64

.;T

Polyphen

0.0040

.;B

Vest4

0.065

MPC

0.19

ClinPred

0.0020

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.022

gMVP

0.21

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over