11-83164259-C-G

Variant summary

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

The NM_001346413.3(PCF11):c.560C>G(p.Thr187Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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: 5.42

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=0.16840413).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCF11	NM_001346413.3	c.560C>G	p.Thr187Ser	missense_variant	4/16	ENST00000690938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCF11	ENST00000690938.1	c.560C>G	p.Thr187Ser	missense_variant	4/16		NM_001346413.3	P3
PCF11	ENST00000298281.8	c.560C>G	p.Thr187Ser	missense_variant	4/16	1		A1
PCF11	ENST00000530304.5	c.560C>G	p.Thr187Ser	missense_variant	4/8	1
PCF11	ENST00000530660.5	c.560C>G	p.Thr187Ser	missense_variant	4/8	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jan 03, 2022

The c.560C>G (p.T187S) alteration is located in exon 4 (coding exon 4) of the PCF11 gene. This alteration results from a C to G substitution at nucleotide position 560, causing the threonine (T) at amino acid position 187 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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0082	T;T;.
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.46	N;.;.
MutationTaster	Benign	0.67	D
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.088
Sift	Benign	0.17	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.012	B;B;.
Vest4		0.13
MutPred		0.12		Gain of phosphorylation at T187 (P = 0.0604);Gain of phosphorylation at T187 (P = 0.0604);Gain of phosphorylation at T187 (P = 0.0604);
MVP		0.28
MPC		0.17
ClinPred		0.37	T
GERP RS		5.6
Varity_R		0.12
gMVP		0.29

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: chr11-82875301;