chr10-110890645-A-G

Variant names:

• chr10-110890645-A-G
• rs143809858
• NM_014456.5:c.965A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_014456.5(PDCD4):​c.965A>G​(p.Gln322Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000204 in 1,609,360 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (1 hom.)
• Consequence: PDCD4 NM_014456.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.30
• Publications: 3 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.042405456).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014456.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD4	NM_014456.5	MANE Select	c.965A>G	p.Gln322Arg	missense	Exon 8 of 12	NP_055271.2
	PDCD4	NM_145341.4		c.932A>G	p.Gln311Arg	missense	Exon 9 of 13	NP_663314.1	Q53EL6-2
	PDCD4	NM_001199492.2		c.923A>G	p.Gln308Arg	missense	Exon 8 of 12	NP_001186421.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD4	ENST00000280154.12	TSL:1 MANE Select	c.965A>G	p.Gln322Arg	missense	Exon 8 of 12	ENSP00000280154.7	Q53EL6-1
	PDCD4	ENST00000393104.6	TSL:1	c.932A>G	p.Gln311Arg	missense	Exon 9 of 13	ENSP00000376816.2	Q53EL6-2
	PDCD4	ENST00000888009.1		c.965A>G	p.Gln322Arg	missense	Exon 8 of 13	ENSP00000558068.1

Frequencies

GnomAD3 genomes AF: 0.000118 AC: 18 AN: 152162 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000717 AC: 18 AN: 251038 AF XY: 0.0000368

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000213 AC: 310 AN: 1457198 Hom.: 1 Cov.: 28 AF XY: 0.000212 AC XY: 154 AN XY: 725286

African (AFR) AF: 0.0000898 AC: 3 AN: 33400

American (AMR) AF: 0.0000224 AC: 1 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86060

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53340

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.000267 AC: 296 AN: 1108036

Other (OTH) AF: 0.000166 AC: 10 AN: 60208

GnomAD4 genome AF: 0.000118 AC: 18 AN: 152162 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74326

African (AFR) AF: 0.000145 AC: 6 AN: 41444

American (AMR) AF: 0.00 AC: 0 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000176 AC: 12 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000133 Hom.: 0

Bravo AF: 0.000110

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000123 AC: 15

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	16
DANN	Benign	0.42
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.25
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.080	N
PhyloP100		3.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	2.7	N
REVEL	Benign	0.064
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.21
MVP		0.27
MPC		0.085
ClinPred		0.049	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.10
gMVP		0.25
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

dbSNP: rs143809858; hg19: chr10-112650403;