Genetic Variant NM_001346413.3:c.1151T>C (chr11-83166048-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001346413.3(PCF11):c.1151T>C(p.Leu384Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PCF11
NM_001346413.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07683492).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346413.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCF11	NM_001346413.3	MANE Select	c.1151T>C	p.Leu384Ser	missense	Exon 5 of 16	NP_001333342.1	A0A8I5KX04
PCF11	NM_001346414.2		c.1151T>C	p.Leu384Ser	missense	Exon 5 of 16	NP_001333343.1
PCF11	NM_015885.4		c.1151T>C	p.Leu384Ser	missense	Exon 5 of 16	NP_056969.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCF11	ENST00000690938.1	MANE Select	c.1151T>C	p.Leu384Ser	missense	Exon 5 of 16	ENSP00000508500.1	A0A8I5KX04
PCF11	ENST00000298281.8	TSL:1	c.1151T>C	p.Leu384Ser	missense	Exon 5 of 16	ENSP00000298281.4	O94913
PCF11	ENST00000530304.5	TSL:1	c.1151T>C	p.Leu384Ser	missense	Exon 5 of 8	ENSP00000431567.1	E9PKN0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1449426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720568

African (AFR)

AF:

0.00

AC:

AN:

32374

American (AMR)

AF:

0.00

AC:

AN:

41324

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25656

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.00

AC:

AN:

82888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53166

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108896

Other (OTH)

AF:

0.00

AC:

AN:

59800

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0047

Eigen

Benign

-0.15

Eigen_PC

Benign

0.075

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.63

M_CAP

Benign

0.0049

MetaRNN

Benign

0.077

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.3

PrimateAI

Benign

0.41

PROVEAN

Benign

0.94

REVEL

Benign

0.075

Sift

Uncertain

0.014

Sift4G

Benign

0.37

Polyphen

0.0080

Vest4

0.18

MutPred

0.19

Gain of phosphorylation at L384 (P = 0.0191)

MVP

0.20

MPC

0.25

ClinPred

0.36

GERP RS

5.9

Varity_R

0.034

gMVP

0.069

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over