Variant chr11-83164216-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001346413.3(PCF11):c.517C>G(p.Pro173Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000623 in 1,606,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PCF11
NM_001346413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.316

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.070492595).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCF11	NM_001346413.3 linkuse as main transcript	c.517C>G	p.Pro173Ala	missense_variant	4/16	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.517C>G	p.Pro173Ala	missense_variant	4/16		NM_001346413.3	ENSP00000508500.1	A0A8I5KX04
PCF11	ENST00000298281.8 linkuse as main transcript	c.517C>G	p.Pro173Ala	missense_variant	4/16	1		ENSP00000298281.4	O94913
PCF11	ENST00000530304.5 linkuse as main transcript	c.517C>G	p.Pro173Ala	missense_variant	4/8	1		ENSP00000431567.1	E9PKN0
PCF11	ENST00000530660.5 linkuse as main transcript	c.517C>G	p.Pro173Ala	missense_variant	4/8	2		ENSP00000434540.1	E9PQ01

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000344

AC:

AN:

1454256

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723310

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000233

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000236

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000642

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

May 15, 2024

The c.517C>G (p.P173A) 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 517, causing the proline (P) at amino acid position 173 to be replaced by an alanine (A). 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

0.050

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.014

T;T;.

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.80

T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.070

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.045

Sift

Uncertain

0.013

D;D;D

Sift4G

Uncertain

0.036

D;T;T

Polyphen

0.018

B;P;.

Vest4

0.080

MutPred

0.18

Loss of glycosylation at P173 (P = 0.0241);Loss of glycosylation at P173 (P = 0.0241);Loss of glycosylation at P173 (P = 0.0241);

MVP

0.17

MPC

0.17

ClinPred

0.51

GERP RS

3.8

Varity_R

0.070

gMVP

0.33

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