Variant 10-110895967-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014456.5(PDCD4):c.1229A>G(p.Asn410Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 1,601,876 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

PDCD4
NM_014456.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44

Variant links:

Genes affected

PDCD4 (HGNC:8763): (programmed cell death 4) This gene is a tumor suppressor and encodes a protein that binds to the eukaryotic translation initiation factor 4A1 and inhibits its function by preventing RNA binding. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

PDCD4 links:

PDCD4 (HGNC:):

PDCD4 links:

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=0.074248284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD4	NM_014456.5 linkuse as main transcript	c.1229A>G	p.Asn410Ser	missense_variant	11/12	ENST00000280154.12	NP_055271.2	Q53EL6-1
PDCD4	NM_145341.4 linkuse as main transcript	c.1196A>G	p.Asn399Ser	missense_variant	12/13		NP_663314.1	Q53EL6-2
PDCD4	NM_001199492.2 linkuse as main transcript	c.1187A>G	p.Asn396Ser	missense_variant	11/12		NP_001186421.1	B4DKX4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD4	ENST00000280154.12 linkuse as main transcript	c.1229A>G	p.Asn410Ser	missense_variant	11/12	1	NM_014456.5	ENSP00000280154.7		Q53EL6-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

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:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000456

AC:

AN:

241024

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

130410

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000313

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000244

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1449674

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

721264

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000633

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

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:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Jul 30, 2024

The c.1229A>G (p.N410S) alteration is located in exon 11 (coding exon 10) of the PDCD4 gene. This alteration results from a A to G substitution at nucleotide position 1229, causing the asparagine (N) at amino acid position 410 to be replaced by a serine (S). 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

0.057

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.13

.;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.0070

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

.;L

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.40

N;N

REVEL

Benign

0.053

Sift

Benign

0.26

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.0

.;B

Vest4

0.082

MutPred

0.32

.;Gain of phosphorylation at N410 (P = 0.0554);

MVP

0.38

MPC

0.064

ClinPred

0.070

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.030

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over