5-272714-C-T

Position:

• chr5-272714-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_013232.4(PDCD6):​c.105C>T​(p.Val35=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,574,744 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (2 hom., cov: 26)
  • Exomes 𝑓: 0.0010 (17 hom.)
• Consequence: PDCD6 NM_013232.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.358

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 5-272714-C-T is Benign according to our data. Variant chr5-272714-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2655242.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.358 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD6	NM_013232.4	c.105C>T	p.Val35=	synonymous_variant	2/6	ENST00000264933.9
PDCD6-AHRR	NR_165159.2	n.180C>T		non_coding_transcript_exon_variant	2/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD6	ENST00000264933.9	c.105C>T	p.Val35=	synonymous_variant	2/6	1	NM_013232.4	P1

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 189 AN: 143952 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.0000286

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000136

Gnomad ASJ AF: 0.000585

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00393

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00208

Gnomad OTH AF: 0.00101

GnomAD3 exomes AF: 0.00142 AC: 314 AN: 221640 Hom.: 3 AF XY: 0.00129 AC XY: 156 AN XY: 121166

Gnomad AFR exome AF: 0.000268

Gnomad AMR exome AF: 0.0000717

Gnomad ASJ exome AF: 0.00222

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00251

Gnomad NFE exome AF: 0.00226

Gnomad OTH exome AF: 0.000937

GnomAD4 exome AF: 0.00103 AC: 1475 AN: 1430696 Hom.: 17 Cov.: 30 AF XY: 0.00106 AC XY: 754 AN XY: 708444

Gnomad4 AFR exome AF: 0.0000673

Gnomad4 AMR exome AF: 0.0000483

Gnomad4 ASJ exome AF: 0.00143

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.00300

Gnomad4 NFE exome AF: 0.00111

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.00131 AC: 189 AN: 144048 Hom.: 2 Cov.: 26 AF XY: 0.00147 AC XY: 103 AN XY: 70272

Gnomad4 AFR AF: 0.0000285

Gnomad4 AMR AF: 0.000136

Gnomad4 ASJ AF: 0.000585

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00393

Gnomad4 NFE AF: 0.00208

Gnomad4 OTH AF: 0.000998

Alfa AF: 0.00241 Hom.: 2

Bravo AF: 0.000718

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PDCD6: BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	7.0
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs145036962; hg19: chr5-272829;