5-271788-C-G

Variant names:

• chr5-271788-C-G
• rs761773860
• NM_013232.4:c.68C>G

Variant summary

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

The NM_013232.4(PDCD6):​c.68C>G​(p.Pro23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,560 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P23L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PDCD6 NM_013232.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82
• 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]

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

ENSG00000286001 (HGNC:):

PDCD6-DT (HGNC:55580): (PDCD6 divergent transcript)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.68C>G	p.Pro23Arg	missense	Exon 1 of 6	NP_037364.1	O75340-1
	PDCD6	NM_001267556.2		c.68C>G	p.Pro23Arg	missense	Exon 1 of 6	NP_001254485.1	O75340-2
	PDCD6	NM_001267557.2		c.68C>G	p.Pro23Arg	missense	Exon 1 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.68C>G	p.Pro23Arg	missense	Exon 1 of 6	ENSP00000264933.4	O75340-1
	PDCD6	ENST00000507528.5	TSL:1	c.68C>G	p.Pro23Arg	missense	Exon 1 of 6	ENSP00000423815.1	O75340-2
	PDCD6	ENST00000509581.5	TSL:1	c.68C>G	p.Pro23Arg	missense	Exon 1 of 3	ENSP00000422691.1	Q86W51

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000838 AC: 1 AN: 119322 AF XY: 0.0000144

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.57e-7 AC: 1 AN: 1321560 Hom.: 0 Cov.: 30 AF XY: 0.00000154 AC XY: 1 AN XY: 651142

African (AFR) AF: 0.00 AC: 0 AN: 26164

American (AMR) AF: 0.00 AC: 0 AN: 24840

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20340

East Asian (EAS) AF: 0.00 AC: 0 AN: 31932

South Asian (SAS) AF: 0.00 AC: 0 AN: 70052

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40394

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3936

European-Non Finnish (NFE) AF: 9.52e-7 AC: 1 AN: 1050184

Other (OTH) AF: 0.00 AC: 0 AN: 53718

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000858 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T
Eigen	Benign	0.12
Eigen_PC	Benign	0.042
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	-0.025	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		1.8
PrimateAI	Pathogenic	0.91	D
PROVEAN	Uncertain	-2.9	D
REVEL	Uncertain	0.48
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.91	P
Vest4		0.37
MutPred		0.40		Loss of loop (P = 9e-04)
MVP		0.77
MPC		0.98
ClinPred		0.97	D
GERP RS		2.3
PromoterAI		-0.053	Neutral
Varity_R		0.45
gMVP		0.67
Mutation Taster		=64/36	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs761773860; hg19: chr5-271903;