rs3756712

chr5-308981-A-Cchr5-308981-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013232.4(PDCD6):c.367+2221A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 154,778 control chromosomes in the GnomAD database, including 21,156 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 0.49 (20757 hom., cov: 34)
  • Exomes 𝑓: 0.54 (399 hom.)
• Consequence: PDCD6 NM_013232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.32

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD6	NM_013232.4	c.367+2221A>C		intron_variant		ENST00000264933.9
PDCD6-AHRR	NR_165159.2	n.283+4760A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD6	ENST00000264933.9	c.367+2221A>C		intron_variant		1	NM_013232.4	P1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75049 AN: 152030 Hom.: 20763 Cov.: 34

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.527

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.648

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.540 AC: 1419 AN: 2630 Hom.: 399 Cov.: 0 AF XY: 0.554 AC XY: 758 AN XY: 1368

Gnomad4 AFR exome AF: 0.391

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.591

Gnomad4 EAS exome AF: 0.236

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 0.618

Gnomad4 NFE exome AF: 0.593

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.493 AC: 75066 AN: 152148 Hom.: 20757 Cov.: 34 AF XY: 0.497 AC XY: 36947 AN XY: 74362

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.260

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.648

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.505

Alfa AF: 0.594 Hom.: 41326

Bravo AF: 0.464

Asia WGS AF: 0.401 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.0
Dann	Benign	0.32

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

Publications

LitVar

Other links and lift over

dbSNP: rs3756712; hg19: chr5-309096;