rs909500893

Variant names:

• chr5-314429-A-G
• rs909500893
• NM_013232.4:c.490A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_013232.4(PDCD6):​c.490A>G​(p.Ile164Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,296 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PDCD6 NM_013232.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.26
• Publications: 0 publications found

Genes affected

PDCD6 (HGNC:8765): (programmed cell death 6) This gene encodes a calcium-binding protein belonging to the penta-EF-hand protein family. Calcium binding is important for homodimerization and for conformational changes required for binding to other protein partners. This gene product participates in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death. In mice deficient for this gene product, however, apoptosis was not blocked suggesting this gene product is functionally redundant. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is also located on the short arm of chromosome 5. [provided by RefSeq, May 2012]

ENSG00000286001 (HGNC:):

PDCD6-AHRR (HGNC:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11502761).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013232.4. 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
	PDCD6	NM_013232.4	MANE Select	c.490A>G	p.Ile164Val	missense	Exon 6 of 6	NP_037364.1	O75340-1
	PDCD6	NM_001267556.2		c.484A>G	p.Ile162Val	missense	Exon 6 of 6	NP_001254485.1	O75340-2
	PDCD6	NM_001267557.2		c.286A>G	p.Ile96Val	missense	Exon 4 of 4	NP_001254486.1	A0A087WZ38

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD6	ENST00000264933.9	TSL:1 MANE Select	c.490A>G	p.Ile164Val	missense	Exon 6 of 6	ENSP00000264933.4	O75340-1
	PDCD6	ENST00000507528.5	TSL:1	c.484A>G	p.Ile162Val	missense	Exon 6 of 6	ENSP00000423815.1	O75340-2
	ENSG00000286001	ENST00000651543.1		n.*2010A>G		non_coding_transcript_exon	Exon 24 of 24	ENSP00000499215.1	A0A494C1T6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460296 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726356

African (AFR) AF: 0.0000299 AC: 1 AN: 33458

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110846

Other (OTH) AF: 0.00 AC: 0 AN: 60334

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.63
DEOGEN2	Benign	0.069	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-2.2	N
PhyloP100		3.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.50	N
REVEL	Benign	0.049
Sift	Benign	0.32	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.054
MutPred		0.52		Loss of helix (P = 0.2271)
MVP		0.30
MPC		0.47
ClinPred		0.18	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.066
gMVP		0.56
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs909500893; hg19: chr5-314544;