Variant 3-167684448-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000392750.7(PDCD10):c.558-59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 934,874 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 15 hom., cov: 31)

Exomes 𝑓: 0.013 ( 110 hom. )

Consequence

PDCD10
ENST00000392750.7 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.22

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-167684448-T-C is Benign according to our data. Variant chr3-167684448-T-C is described in ClinVar as [Benign]. Clinvar id is 1183837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.011 (1681/152138) while in subpopulation AMR AF= 0.0181 (276/15274). AF 95% confidence interval is 0.0163. There are 15 homozygotes in gnomad4. There are 764 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1681 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDCD10	NM_007217.4 linkuse as main transcript	c.558-59A>G		intron_variant		ENST00000392750.7	NP_009148.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDCD10	ENST00000392750.7 linkuse as main transcript	c.558-59A>G		intron_variant		1	NM_007217.4	ENSP00000376506	P1

Frequencies

GnomAD3 genomes

AF:

0.0111

AC:

1681

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0294

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0162

Gnomad OTH

AF:

0.0163

GnomAD4 exome

AF:

0.0134

AC:

10511

AN:

782736

Hom.:

110

AF XY:

0.0133

AC XY:

5521

AN XY:

416438

show subpopulations

Gnomad4 AFR exome

AF:

0.00361

Gnomad4 AMR exome

AF:

0.0132

Gnomad4 ASJ exome

AF:

0.0280

Gnomad4 EAS exome

AF:

0.0000549

Gnomad4 SAS exome

AF:

0.00402

Gnomad4 FIN exome

AF:

0.00260

Gnomad4 NFE exome

AF:

0.0163

Gnomad4 OTH exome

AF:

0.0157

GnomAD4 genome

AF:

0.0110

AC:

1681

AN:

152138

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

764

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00332

Gnomad4 AMR

AF:

0.0181

Gnomad4 ASJ

AF:

0.0294

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.0162

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over