chr3-167684221-T-A

Variant names:

• chr3-167684221-T-A
• rs886058161
• NM_007217.4:c.*87A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007217.4(PDCD10):​c.*87A>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00000319 in 627,340 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 Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: PDCD10 NM_007217.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.73
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).

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.*87A>T		3_prime_UTR	Exon 9 of 9	NP_009148.2
	PDCD10	NM_001439202.1		c.*87A>T		3_prime_UTR	Exon 9 of 9	NP_001426131.1
	PDCD10	NM_001439204.1		c.*87A>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.*87A>T		3_prime_UTR	Exon 9 of 9	ENSP00000376506.2	Q9BUL8
	PDCD10	ENST00000473645.6	TSL:1	c.*87A>T		3_prime_UTR	Exon 9 of 9	ENSP00000418317.2	Q9BUL8
	PDCD10	ENST00000497056.6	TSL:1	c.*87A>T		3_prime_UTR	Exon 8 of 8	ENSP00000420553.2	Q9BUL8

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000319 AC: 2 AN: 627340 Hom.: 0 Cov.: 8 AF XY: 0.00000588 AC XY: 2 AN XY: 340208

African (AFR) AF: 0.00 AC: 0 AN: 17616

American (AMR) AF: 0.00 AC: 0 AN: 41384

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20368

East Asian (EAS) AF: 0.00 AC: 0 AN: 35124

South Asian (SAS) AF: 0.00 AC: 0 AN: 68026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2922

European-Non Finnish (NFE) AF: 0.00000552 AC: 2 AN: 362504

Other (OTH) AF: 0.00 AC: 0 AN: 32266

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	-0.42
CADD	Benign	19
DANN	Benign	0.92
PhyloP100		6.7

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: rs886058161; hg19: chr3-167402009;