11-83166033-C-A

Variant names:

• chr11-83166033-C-A
• NM_001346413.3:c.1136C>A

Variant summary

Our verdict is Uncertain significance. The variant received 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. Variant has been reported in ClinVar as Uncertain significance (★).

• 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
• Publications: 0 publications found

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

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=0.16820055).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCF11	NM_001346413.3	MANE Select	c.1136C>A	p.Ser379Tyr	missense	Exon 5 of 16	NP_001333342.1	A0A8I5KX04
	PCF11	NM_001346414.2		c.1136C>A	p.Ser379Tyr	missense	Exon 5 of 16	NP_001333343.1
	PCF11	NM_015885.4		c.1136C>A	p.Ser379Tyr	missense	Exon 5 of 16	NP_056969.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCF11	ENST00000690938.1	MANE Select	c.1136C>A	p.Ser379Tyr	missense	Exon 5 of 16	ENSP00000508500.1	A0A8I5KX04
	PCF11	ENST00000298281.8	TSL:1	c.1136C>A	p.Ser379Tyr	missense	Exon 5 of 16	ENSP00000298281.4	O94913
	PCF11	ENST00000530304.5	TSL:1	c.1136C>A	p.Ser379Tyr	missense	Exon 5 of 8	ENSP00000431567.1	E9PKN0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.64	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.5	L
PhyloP100		2.5
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.16
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.013	D
Polyphen		0.98	D
Vest4		0.30
MutPred		0.17		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
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

hg19: chr11-82877075;