rs864309498

Variant names:

• chr11-83169557-GT-G
• rs864309498
• NM_001346413.3:c.3618delT

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_001346413.3(PCF11):​c.3618delT​(p.Phe1206LeufsTer136) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCF11 NM_001346413.3 frameshift
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 3.44
• Publications: 1 publications found

Genes affected

PCF11 (HGNC:30097): (PCF11 cleavage and polyadenylation factor subunit) The protein encoded by this gene binds to CLP1 to form pre-mRNA cleavage factor IIm. The encoded protein is necessary for efficient Pol II transcription termination and may be involved in degradation of the 3' product of polyA site cleavage. [provided by RefSeq, Oct 2016]

ACMG classification

Our verdict: Pathogenic. The variant received 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346413.3. 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
	PCF11	NM_001346413.3	MANE Select	c.3618delT	p.Phe1206LeufsTer136	frameshift	Exon 8 of 16	NP_001333342.1
	PCF11	NM_001346414.2		c.3618delT	p.Phe1206LeufsTer136	frameshift	Exon 8 of 16	NP_001333343.1
	PCF11	NM_015885.4		c.3225delT	p.Phe1075LeufsTer136	frameshift	Exon 8 of 16	NP_056969.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCF11	ENST00000690938.1	MANE Select	c.3618delT	p.Phe1206LeufsTer136	frameshift	Exon 8 of 16	ENSP00000508500.1
	PCF11	ENST00000298281.8	TSL:1	c.3225delT	p.Phe1075LeufsTer136	frameshift	Exon 8 of 16	ENSP00000298281.4
	PCF11	ENST00000932062.1		c.3240delT	p.Phe1080LeufsTer136	frameshift	Exon 8 of 16	ENSP00000602121.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	1	-	Acute megakaryoblastic leukemia;C1334655:Mediastinal germ cell tumor (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs864309498; hg19: chr11-82880599;