rs3792293

chr3-167734716-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007217.4(PDCD10):c.-308T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 154,570 control chromosomes in the GnomAD database, including 7,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.30 (7355 hom., cov: 33)
  • Exomes 𝑓: 0.26 (96 hom.)
• Consequence: PDCD10 NM_007217.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.18

Genes affected

PDCD10 (HGNC:8761): (programmed cell death 10) This gene encodes an evolutionarily conserved protein associated with cell apoptosis. The protein interacts with the serine/threonine protein kinase MST4 to modulate the extracellular signal-regulated kinase (ERK) pathway. It also interacts with and is phosphoryated by serine/threonine kinase 25, and is thought to function in a signaling pathway essential for vascular developent. Mutations in this gene are one cause of cerebral cavernous malformations, which are vascular malformations that cause seizures and cerebral hemorrhages. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-167734716-A-G is Benign according to our data. Variant chr3-167734716-A-G is described in ClinVar as [Benign]. Clinvar id is 590668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDCD10	NM_007217.4	c.-308T>C		5_prime_UTR_variant	1/9	ENST00000392750.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDCD10	ENST00000392750.7	c.-308T>C		5_prime_UTR_variant	1/9	1	NM_007217.4	P1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45593 AN: 152128 Hom.: 7339 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.190

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.256

GnomAD4 exome AF: 0.257 AC: 597 AN: 2324 Hom.: 96 Cov.: 0 AF XY: 0.254 AC XY: 427 AN XY: 1684

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.184

Gnomad4 FIN exome AF: 0.324

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.310

GnomAD4 genome AF: 0.300 AC: 45640 AN: 152246 Hom.: 7355 Cov.: 33 AF XY: 0.297 AC XY: 22084 AN XY: 74430

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.257

Alfa AF: 0.261 Hom.: 6814

Bravo AF: 0.295

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 02, 2018

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 17, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.3
Dann	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs3792293; hg19: chr3-167452504; COSMIC: COSV55507798; COSMIC: COSV55507798;