11-83163805-C-T

Variant names:

• chr11-83163805-C-T
• NM_001346413.3:c.445C>T

Variant summary

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

The NM_001346413.3(PCF11):​c.445C>T​(p.Pro149Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.72

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCF11	NM_001346413.3	c.445C>T	p.Pro149Ser	missense_variant	Exon 3 of 16	ENST00000690938.1	NP_001333342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCF11	ENST00000690938.1	c.445C>T	p.Pro149Ser	missense_variant	Exon 3 of 16		NM_001346413.3	ENSP00000508500.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 26

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 20, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.445C>T (p.P149S) alteration is located in exon 3 (coding exon 3) of the PCF11 gene. This alteration results from a C to T substitution at nucleotide position 445, causing the proline (P) at amino acid position 149 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	Pathogenic	0.95
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T;.
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.4	M;.;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-2.4	N;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.019	D;D;D
Sift4G	Uncertain	0.014	D;D;D
Polyphen		1.0	D;B;.
Vest4		0.53
MutPred		0.34		Loss of catalytic residue at P149 (P = 0.0056);Loss of catalytic residue at P149 (P = 0.0056);Loss of catalytic residue at P149 (P = 0.0056);
MVP		0.47
MPC		0.32
ClinPred		0.75	D
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.64

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: chr11-82874847;