5-287899-T-G

Variant names:

• chr5-287899-T-G
• rs4957014
• NM_013232.4:c.163+15127T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013232.4(PDCD6):​c.163+15127T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,096 control chromosomes in the GnomAD database, including 41,511 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 0.73 (41511 hom., cov: 33)
• Consequence: PDCD6 NM_013232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.442
• Publications: 16 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD6	NM_013232.4	c.163+15127T>G		intron_variant	Intron 2 of 5	ENST00000264933.9	NP_037364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD6	ENST00000264933.9	c.163+15127T>G		intron_variant	Intron 2 of 5	1	NM_013232.4	ENSP00000264933.4
ENSG00000286001	ENST00000651543.1	n.*1533+15127T>G		intron_variant	Intron 19 of 23			ENSP00000499215.1
PDCD6-AHRR	ENST00000675395.1	n.163+15127T>G		intron_variant	Intron 2 of 13			ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.734 AC: 111526 AN: 151978 Hom.: 41475 Cov.: 33

Gnomad AFR AF: 0.777

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.707

Gnomad ASJ AF: 0.701

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.732

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.752

Gnomad OTH AF: 0.732

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.734 AC: 111623 AN: 152096 Hom.: 41511 Cov.: 33 AF XY: 0.730 AC XY: 54290 AN XY: 74338

African (AFR) AF: 0.777 AC: 32241 AN: 41482

American (AMR) AF: 0.706 AC: 10797 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.701 AC: 2431 AN: 3470

East Asian (EAS) AF: 0.314 AC: 1622 AN: 5172

South Asian (SAS) AF: 0.670 AC: 3227 AN: 4820

European-Finnish (FIN) AF: 0.732 AC: 7739 AN: 10574

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.752 AC: 51093 AN: 67972

Other (OTH) AF: 0.729 AC: 1542 AN: 2114

Alfa AF: 0.737 Hom.: 6705

Bravo AF: 0.730

Asia WGS AF: 0.514 AC: 1789 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs4957014; hg19: chr5-288014;