dbSNP rs748153515: PDCD10:c.96+4988C>G (chr3-167715074-G-C) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_007217.4(PDCD10):c.96+4988C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000389 in 151,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Consequence

PDCD10
NM_007217.4 intron

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.365

Publications

0 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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000389 (59/151546) while in subpopulation NFE AF = 0.000709 (48/67710). AF 95% confidence interval is 0.000549. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDCD10	NM_007217.4 link	c.96+4988C>G		intron_variant	Intron 3 of 8	ENST00000392750.7	NP_009148.2	Q9BUL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD10	ENST00000392750.7 link	c.96+4988C>G		intron_variant	Intron 3 of 8	1	NM_007217.4	ENSP00000376506.2		Q9BUL8

Frequencies

GnomAD3 genomes

AF:

0.000390

AC:

AN:

151430

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000170

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000709

Gnomad OTH

AF:

0.000481

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.000389

AC:

AN:

151546

Hom.:

Cov.:

AF XY:

0.000365

AC XY:

AN XY:

74064

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41378

American (AMR)

AF:

0.000197

AC:

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10506

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000709

AC:

AN:

67710

Other (OTH)

AF:

0.000476

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000212

Hom.:

Bravo

AF:

0.000295

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

Cerebral cavernous malformation 3

Other:1

May 15, 2017

Institute of Human Genetics Greifswald, Research Division, University Medicine Greifswald

Significance:not provided

Review Status:no classification provided

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.8

(source)

DANN

Benign

0.57

PhyloP100

0.36

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