rs763092811

Variant names:

• chr10-110881416-C-G
• rs763092811
• NM_014456.5:c.227C>G

Your query was ambiguous. Multiple possible variants found:

• chr10-110881416-C-G
• chr10-110881416-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_014456.5(PDCD4):​c.227C>G​(p.Ser76Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S76L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PDCD4 NM_014456.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.84
• Publications: 0 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: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.759

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.227C>G	p.Ser76Trp	missense	Exon 3 of 12	NP_055271.2
	PDCD4	NM_145341.4		c.194C>G	p.Ser65Trp	missense	Exon 4 of 13	NP_663314.1	Q53EL6-2
	PDCD4	NM_001199492.2		c.185C>G	p.Ser62Trp	missense	Exon 3 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.227C>G	p.Ser76Trp	missense	Exon 3 of 12	ENSP00000280154.7	Q53EL6-1
	PDCD4	ENST00000393104.6	TSL:1	c.194C>G	p.Ser65Trp	missense	Exon 4 of 13	ENSP00000376816.2	Q53EL6-2
	PDCD4	ENST00000888009.1		c.227C>G	p.Ser76Trp	missense	Exon 3 of 13	ENSP00000558068.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Uncertain	0.080	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.63	D
Eigen	Pathogenic	0.84
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.074	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.8
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.37		Loss of phosphorylation at S76 (P = 7e-04)
MVP		0.72
MPC		0.52
ClinPred		0.98	D
GERP RS		5.7
Varity_R		0.45
gMVP		0.48
Mutation Taster		=33/67	disease causing

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: rs763092811; hg19: chr10-112641174;