Variant chr11-83165679-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001346413.3(PCF11):c.782T>C(p.Ile261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,613,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

PCF11
NM_001346413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

Variant links:

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]

PCF11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.049958825).

BS2

High AC in GnomAd4 at 29 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCF11	NM_001346413.3 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	5/16	ENST00000690938.1	NP_001333342.1	A0A8I5KX04

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PCF11	ENST00000690938.1 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	5/16		NM_001346413.3	ENSP00000508500.1	A0A8I5KX04
PCF11	ENST00000298281.8 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	5/16	1		ENSP00000298281.4	O94913
PCF11	ENST00000530304.5 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	5/8	1		ENSP00000431567.1	E9PKN0
PCF11	ENST00000530660.5 linkuse as main transcript	c.782T>C	p.Ile261Thr	missense_variant	5/8	2		ENSP00000434540.1	E9PQ01

Frequencies

GnomAD3 genomes

AF:

0.000191

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000153

AC:

AN:

248996

Hom.:

AF XY:

0.000133

AC XY:

AN XY:

135080

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000292

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000339

AC:

495

AN:

1461400

Hom.:

Cov.:

AF XY:

0.000341

AC XY:

248

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.000398

GnomAD4 genome

AF:

0.000191

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000289

Hom.:

Bravo

AF:

0.000181

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000244

AC:

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000297

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.782T>C (p.I261T) alteration is located in exon 5 (coding exon 5) of the PCF11 gene. This alteration results from a T to C substitution at nucleotide position 782, causing the isoleucine (I) at amino acid position 261 to be replaced by a threonine (T). 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

0.20

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0098

T;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.050

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.32

N;.;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.57

N;N;N

REVEL

Benign

0.018

Sift

Benign

0.53

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0050

B;B;.

Vest4

0.19

MVP

0.19

MPC

0.22

ClinPred

0.053

GERP RS

3.4

Varity_R

0.079

gMVP

0.081

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over