rs34104444

Positions:

• chr10-110885330-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014456.5(PDCD4):​c.519G>A​(p.Gln173Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 1,588,624 control chromosomes in the GnomAD database, including 1,863 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.058 (329 hom., cov: 32)
  • Exomes 𝑓: 0.043 (1534 hom.)
• Consequence: PDCD4 NM_014456.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.16

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=3.16 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD4	NM_014456.5	c.519G>A	p.Gln173Gln	synonymous_variant	5/12	ENST00000280154.12	NP_055271.2
PDCD4	NM_145341.4	c.486G>A	p.Gln162Gln	synonymous_variant	6/13		NP_663314.1
PDCD4	NM_001199492.2	c.477G>A	p.Gln159Gln	synonymous_variant	5/12		NP_001186421.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD4	ENST00000280154.12	c.519G>A	p.Gln173Gln	synonymous_variant	5/12	1	NM_014456.5	ENSP00000280154.7

Frequencies

GnomAD3 genomes AF: 0.0579 AC: 8800 AN: 152032 Hom.: 330 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.0154

Gnomad AMR AF: 0.0299

Gnomad ASJ AF: 0.0674

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00850

Gnomad FIN AF: 0.0545

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0437

Gnomad OTH AF: 0.0498

GnomAD3 exomes AF: 0.0375 AC: 9162 AN: 244490 Hom.: 229 AF XY: 0.0359 AC XY: 4753 AN XY: 132448

Gnomad AFR exome AF: 0.103

Gnomad AMR exome AF: 0.0231

Gnomad ASJ exome AF: 0.0678

Gnomad EAS exome AF: 0.000225

Gnomad SAS exome AF: 0.0105

Gnomad FIN exome AF: 0.0500

Gnomad NFE exome AF: 0.0404

Gnomad OTH exome AF: 0.0401

GnomAD4 exome AF: 0.0426 AC: 61212 AN: 1436474 Hom.: 1534 Cov.: 25 AF XY: 0.0413 AC XY: 29554 AN XY: 715900

Gnomad4 AFR exome AF: 0.110

Gnomad4 AMR exome AF: 0.0253

Gnomad4 ASJ exome AF: 0.0672

Gnomad4 EAS exome AF: 0.0000770

Gnomad4 SAS exome AF: 0.0113

Gnomad4 FIN exome AF: 0.0477

Gnomad4 NFE exome AF: 0.0441

Gnomad4 OTH exome AF: 0.0475

GnomAD4 genome AF: 0.0578 AC: 8801 AN: 152150 Hom.: 329 Cov.: 32 AF XY: 0.0562 AC XY: 4180 AN XY: 74378

Gnomad4 AFR AF: 0.106

Gnomad4 AMR AF: 0.0298

Gnomad4 ASJ AF: 0.0674

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00767

Gnomad4 FIN AF: 0.0545

Gnomad4 NFE AF: 0.0437

Gnomad4 OTH AF: 0.0492

Alfa AF: 0.0518 Hom.: 140

Bravo AF: 0.0581

Asia WGS AF: 0.0100 AC: 37 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	6.9
DANN	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs34104444; hg19: chr10-112645088;