11-83157508-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001346413.3(PCF11):c.69G>T(p.Gln23His) 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. 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: 3.81

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27214158).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCF11	NM_001346413.3	c.69G>T	p.Gln23His	missense_variant	1/16	ENST00000690938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCF11	ENST00000690938.1	c.69G>T	p.Gln23His	missense_variant	1/16		NM_001346413.3	P3

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

Aug 08, 2022

The c.69G>T (p.Q23H) alteration is located in exon 1 (coding exon 1) of the PCF11 gene. This alteration results from a G to T substitution at nucleotide position 69, causing the glutamine (Q) at amino acid position 23 to be replaced by a histidine (H). 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	0.96
BayesDel_addAF	Benign	-0.085	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.058	T;T;.;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.78	T;D;D;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.0	M;.;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.011	D;D;D;T
Sift4G	Uncertain	0.0040	D;D;D;T
Polyphen		0.99	D;B;.;.
Vest4		0.29
MutPred		0.34		Gain of catalytic residue at Q23 (P = 0.1019);Gain of catalytic residue at Q23 (P = 0.1019);Gain of catalytic residue at Q23 (P = 0.1019);Gain of catalytic residue at Q23 (P = 0.1019);
MVP		0.71
MPC		2.6
ClinPred		0.92	D
GERP RS		1.9
Varity_R		0.12
gMVP		0.69

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: chr11-82868550;