11-83165744-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346413.3(PCF11):c.847C>T(p.Pro283Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCF11 NM_001346413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.48

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.110153615).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCF11	NM_001346413.3	c.847C>T	p.Pro283Ser	missense_variant	5/16	ENST00000690938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCF11	ENST00000690938.1	c.847C>T	p.Pro283Ser	missense_variant	5/16		NM_001346413.3	P3
PCF11	ENST00000298281.8	c.847C>T	p.Pro283Ser	missense_variant	5/16	1		A1
PCF11	ENST00000530304.5	c.847C>T	p.Pro283Ser	missense_variant	5/8	1
PCF11	ENST00000530660.5	c.847C>T	p.Pro283Ser	missense_variant	5/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 25, 2023

The c.847C>T (p.P283S) alteration is located in exon 5 (coding exon 5) of the PCF11 gene. This alteration results from a C to T substitution at nucleotide position 847, causing the proline (P) at amino acid position 283 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
Cadd	Benign	19
Dann	Uncertain	0.99
DEOGEN2	Benign	0.025	T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.030
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.81	L;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.4	N;N;N
REVEL	Benign	0.029
Sift	Benign	0.069	T;T;T
Sift4G	Benign	0.21	T;T;T
Polyphen		0.0010	B;B;.
Vest4		0.21
MutPred		0.17		Gain of phosphorylation at P283 (P = 0.0145);Gain of phosphorylation at P283 (P = 0.0145);Gain of phosphorylation at P283 (P = 0.0145);
MVP		0.31
MPC		0.18
ClinPred		0.18	T
GERP RS		3.7
Varity_R		0.083
gMVP		0.34

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-82876786;