5-308981-A-C

Variant names:

• chr5-308981-A-C
• rs3756712
• NM_013232.4:c.367+2221A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 27 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:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PDCD6	NM_013232.4	c.367+2221A>C		intron_variant	Intron 4 of 5	ENST00000264933.9	NP_037364.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD6	ENST00000264933.9	c.367+2221A>C		intron_variant	Intron 4 of 5	1	NM_013232.4	ENSP00000264933.4
ENSG00000286001	ENST00000651543.1	n.*1737+2221A>C		intron_variant	Intron 21 of 23			ENSP00000499215.1
PDCD6-AHRR	ENST00000675395.1	n.208+4760A>C		intron_variant	Intron 3 of 13			ENSP00000502570.1

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

African (AFR) AF: 0.391 AC: 18 AN: 46

American (AMR) AF: 0.500 AC: 15 AN: 30

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 26 AN: 44

East Asian (EAS) AF: 0.236 AC: 83 AN: 352

South Asian (SAS) AF: 0.833 AC: 10 AN: 12

European-Finnish (FIN) AF: 0.618 AC: 199 AN: 322

Middle Eastern (MID) AF: 0.357 AC: 5 AN: 14

European-Non Finnish (NFE) AF: 0.593 AC: 995 AN: 1678

Other (OTH) AF: 0.515 AC: 68 AN: 132

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

African (AFR) AF: 0.250 AC: 10372 AN: 41506

American (AMR) AF: 0.496 AC: 7571 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1866 AN: 3472

East Asian (EAS) AF: 0.260 AC: 1347 AN: 5180

South Asian (SAS) AF: 0.583 AC: 2817 AN: 4830

European-Finnish (FIN) AF: 0.648 AC: 6844 AN: 10566

Middle Eastern (MID) AF: 0.384 AC: 113 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42589 AN: 68000

Other (OTH) AF: 0.505 AC: 1066 AN: 2112

Alfa AF: 0.577 Hom.: 98068

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
PhyloP100		-2.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs3756712; hg19: chr5-309096;