Variant 11-83166528-C-T 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.1631C>T(p.Ala544Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,613,634 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

PCF11
NM_001346413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.07

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=0.057198524).

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCF11	NM_001346413.3 linkuse as main transcript	c.1631C>T	p.Ala544Val	missense_variant	5/16	ENST00000690938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
PCF11	ENST00000690938.1 linkuse as main transcript	c.1631C>T	p.Ala544Val	missense_variant	5/16		NM_001346413.3	P3
PCF11	ENST00000298281.8 linkuse as main transcript	c.1631C>T	p.Ala544Val	missense_variant	5/16	1		A1
PCF11	ENST00000530304.5 linkuse as main transcript	c.1631C>T	p.Ala544Val	missense_variant	5/8	1
PCF11	ENST00000530660.5 linkuse as main transcript	c.1631C>T	p.Ala544Val	missense_variant	5/8	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152042

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000803

AC:

AN:

248918

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135046

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:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461592

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.00000720

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74258

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:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00000828

AC:

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

Sep 20, 2023

The c.1631C>T (p.A544V) 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 1631, causing the alanine (A) at amino acid position 544 to be replaced by a valine (V). 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

0.072

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0086

T;T;.

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.64

T;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

0.030

N;N;N

REVEL

Benign

0.071

Sift

Benign

0.18

T;T;T

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0020

B;B;.

Vest4

0.074

MVP

0.27

MPC

0.17

ClinPred

0.077

GERP RS

4.1

Varity_R

0.039

gMVP

0.092

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