dbSNP rs3792293: PDCD10:c.-308T>C (chr3-167734716-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.18

Publications

10 publications found

Variant links:

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]

PDCD10 Gene-Disease associations (from GenCC):

cerebral cavernous malformation 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
famililal cerebral cavernous malformations
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PDCD10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PDCD10	NM_007217.4 link	c.-308T>C		5_prime_UTR_variant	Exon 1 of 9	ENST00000392750.7	NP_009148.2	Q9BUL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD10	ENST00000392750.7 link	c.-308T>C		5_prime_UTR_variant	Exon 1 of 9	1	NM_007217.4	ENSP00000376506.2		Q9BUL8

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45593

AN:

152128

Hom.:

7339

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.254

AC XY:

427

AN XY:

1684

show subpopulations

African (AFR)

AF:

0.333

AC:

AN:

American (AMR)

AF:

0.357

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.203

AC:

AN:

South Asian (SAS)

AF:

0.184

AC:

AN:

European-Finnish (FIN)

AF:

0.324

AC:

140

AN:

432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.242

AC:

393

AN:

1626

Other (OTH)

AF:

0.310

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.300

AC:

45640

AN:

152246

Hom.:

7355

Cov.:

AF XY:

0.297

AC XY:

22084

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.426

AC:

17687

AN:

41538

American (AMR)

AF:

0.186

AC:

2853

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

557

AN:

3472

East Asian (EAS)

AF:

0.302

AC:

1558

AN:

5162

South Asian (SAS)

AF:

0.126

AC:

607

AN:

4832

European-Finnish (FIN)

AF:

0.317

AC:

3359

AN:

10604

Middle Eastern (MID)

AF:

0.146

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.268

AC:

18260

AN:

68016

Other (OTH)

AF:

0.257

AC:

543

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1703

3407

5110

6814

8517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

450

900

1350

1800

2250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.273

Hom.:

20538

Bravo

AF:

0.295

Asia WGS

AF:

0.223

AC:

776

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 17, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Apr 02, 2018

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.3

(source)

DANN

Benign

0.64

PhyloP100

-1.2

PromoterAI

0.032

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over