11-83166048-T-C

Variant names:

• chr11-83166048-T-C
• NM_001346413.3:c.1151T>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/21 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.31

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07683492).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCF11	NM_001346413.3	c.1151T>C	p.Leu384Ser	missense_variant	Exon 5 of 16	ENST00000690938.1	NP_001333342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCF11	ENST00000690938.1	c.1151T>C	p.Leu384Ser	missense_variant	Exon 5 of 16		NM_001346413.3	ENSP00000508500.1
PCF11	ENST00000298281.8	c.1151T>C	p.Leu384Ser	missense_variant	Exon 5 of 16	1		ENSP00000298281.4
PCF11	ENST00000530304.5	c.1151T>C	p.Leu384Ser	missense_variant	Exon 5 of 8	1		ENSP00000431567.1
PCF11	ENST00000530660.5	c.1151T>C	p.Leu384Ser	missense_variant	Exon 5 of 8	2		ENSP00000434540.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449426 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 720568

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1151T>C (p.L384S) 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 1151, causing the leucine (L) at amino acid position 384 to be replaced by a serine (S). 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	0.088
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0047	T;T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	0.075
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.63	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.077	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.94	N;N;N
REVEL	Benign	0.075
Sift	Uncertain	0.014	D;D;D
Sift4G	Benign	0.37	T;T;T
Polyphen		0.0080	B;B;.
Vest4		0.18
MutPred		0.19		Gain of phosphorylation at L384 (P = 0.0191);Gain of phosphorylation at L384 (P = 0.0191);Gain of phosphorylation at L384 (P = 0.0191);
MVP		0.20
MPC		0.25
ClinPred		0.36	T
GERP RS		5.9
Varity_R		0.034
gMVP		0.069

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-82877090;