chr11-83166033-C-A

Position:

• chr11-83166033-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001346413.3(PCF11):​c.1136C>A​(p.Ser379Tyr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PCF11 NM_001346413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.53

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=0.16820055).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCF11	NM_001346413.3	c.1136C>A	p.Ser379Tyr	missense_variant	5/16	ENST00000690938.1	NP_001333342.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCF11	ENST00000690938.1	c.1136C>A	p.Ser379Tyr	missense_variant	5/16		NM_001346413.3	ENSP00000508500.1
PCF11	ENST00000298281.8	c.1136C>A	p.Ser379Tyr	missense_variant	5/16	1		ENSP00000298281.4
PCF11	ENST00000530304.5	c.1136C>A	p.Ser379Tyr	missense_variant	5/8	1		ENSP00000431567.1
PCF11	ENST00000530660.5	c.1136C>A	p.Ser379Tyr	missense_variant	5/8	2		ENSP00000434540.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 07, 2024

The c.1136C>A (p.S379Y) alteration is located in exon 5 (coding exon 5) of the PCF11 gene. This alteration results from a C to A substitution at nucleotide position 1136, causing the serine (S) at amino acid position 379 to be replaced by a tyrosine (Y). 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	0.19
BayesDel_addAF	Benign	-0.037	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T;T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L;.;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.98	D;D;.
Vest4		0.30
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);Loss of relative solvent accessibility (P = 0.0676);
MVP		0.48
MPC		0.62
ClinPred		0.86	D
GERP RS		5.9
Varity_R		0.18
gMVP		0.052

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: chr11-82877075;