dbSNP rs1244988643: PCF11:p.Ser254Tyr (chr11-83165658-C-A) – 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.761C>A(p.Ser254Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S254F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PCF11
NM_001346413.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.52

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=0.25742006).

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.761C>A	p.Ser254Tyr	missense	Exon 5 of 16	NP_001333342.1	A0A8I5KX04
PCF11	NM_001346414.2		c.761C>A	p.Ser254Tyr	missense	Exon 5 of 16	NP_001333343.1
PCF11	NM_015885.4		c.761C>A	p.Ser254Tyr	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.761C>A	p.Ser254Tyr	missense	Exon 5 of 16	ENSP00000508500.1	A0A8I5KX04
PCF11	ENST00000298281.8	TSL:1	c.761C>A	p.Ser254Tyr	missense	Exon 5 of 16	ENSP00000298281.4	O94913
PCF11	ENST00000530304.5	TSL:1	c.761C>A	p.Ser254Tyr	missense	Exon 5 of 8	ENSP00000431567.1	E9PKN0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248914

AF XY:

0.00000740

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 FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461350

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726960

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.0000750

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111652

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

0.0099

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.84

M_CAP

Benign

0.013

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.8

PhyloP100

3.5

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-2.2

REVEL

Benign

0.078

Sift

Uncertain

0.0090

Sift4G

Benign

0.064

Polyphen

0.99

Vest4

0.54

MutPred

0.33

Gain of catalytic residue at S254 (P = 0.0024)

MVP

0.40

MPC

0.69

ClinPred

0.72

GERP RS

5.7

Varity_R

0.19

gMVP

0.29

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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