rs190941416

Variant names:

• chr3-167684023-C-A
• rs190941416
• NM_007217.4:c.*285G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_007217.4(PDCD10):​c.*285G>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00242 in 275,274 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (3 hom.)
• Consequence: PDCD10 NM_007217.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.13
• Publications: 0 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 3-167684023-C-A is Benign according to our data. Variant chr3-167684023-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 344102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00236 (358/151920) while in subpopulation NFE AF = 0.00379 (257/67896). AF 95% confidence interval is 0.0034. There are 0 homozygotes in GnomAd4. There are 163 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 358 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007217.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD10	NM_007217.4	MANE Select	c.*285G>T		3_prime_UTR	Exon 9 of 9	NP_009148.2
	PDCD10	NM_001439202.1		c.*285G>T		3_prime_UTR	Exon 9 of 9	NP_001426131.1
	PDCD10	NM_001439204.1		c.*285G>T		3_prime_UTR	Exon 8 of 8	NP_001426133.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDCD10	ENST00000392750.7	TSL:1 MANE Select	c.*285G>T		3_prime_UTR	Exon 9 of 9	ENSP00000376506.2	Q9BUL8
	PDCD10	ENST00000473645.6	TSL:1	c.*285G>T		3_prime_UTR	Exon 9 of 9	ENSP00000418317.2	Q9BUL8
	PDCD10	ENST00000497056.6	TSL:1	c.*285G>T		3_prime_UTR	Exon 8 of 8	ENSP00000420553.2	Q9BUL8

Frequencies

GnomAD3 genomes AF: 0.00236 AC: 358 AN: 151804 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000853

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00580

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00378

Gnomad OTH AF: 0.00337

GnomAD4 exome AF: 0.00249 AC: 307 AN: 123354 Hom.: 3 Cov.: 0 AF XY: 0.00251 AC XY: 164 AN XY: 65274

African (AFR) AF: 0.000911 AC: 4 AN: 4392

American (AMR) AF: 0.000852 AC: 5 AN: 5870

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3604

East Asian (EAS) AF: 0.00 AC: 0 AN: 8532

South Asian (SAS) AF: 0.000262 AC: 4 AN: 15270

European-Finnish (FIN) AF: 0.00515 AC: 27 AN: 5246

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 526

European-Non Finnish (NFE) AF: 0.00343 AC: 250 AN: 72794

Other (OTH) AF: 0.00239 AC: 17 AN: 7120

GnomAD4 genome AF: 0.00236 AC: 358 AN: 151920 Hom.: 0 Cov.: 31 AF XY: 0.00220 AC XY: 163 AN XY: 74204

African (AFR) AF: 0.000458 AC: 19 AN: 41472

American (AMR) AF: 0.000851 AC: 13 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00580 AC: 61 AN: 10514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00379 AC: 257 AN: 67896

Other (OTH) AF: 0.00333 AC: 7 AN: 2100

Alfa AF: 0.00328 Hom.: 0

Bravo AF: 0.00203

Asia WGS AF: 0.00115 AC: 4 AN: 3476

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Cerebral cavernous malformation 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	19
DANN	Benign	0.88
PhyloP100		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs190941416; hg19: chr3-167401811;