chr11-83164259-C-G

Variant names:

• chr11-83164259-C-G
• NM_001346413.3:c.560C>G

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.560C>G​(p.Thr187Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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)
• Consequence: PCF11 NM_001346413.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.42
• 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=0.16840413).

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.560C>G	p.Thr187Ser	missense	Exon 4 of 16	NP_001333342.1	A0A8I5KX04
	PCF11	NM_001346414.2		c.560C>G	p.Thr187Ser	missense	Exon 4 of 16	NP_001333343.1
	PCF11	NM_015885.4		c.560C>G	p.Thr187Ser	missense	Exon 4 of 16	NP_056969.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCF11	ENST00000690938.1	MANE Select	c.560C>G	p.Thr187Ser	missense	Exon 4 of 16	ENSP00000508500.1	A0A8I5KX04
	PCF11	ENST00000298281.8	TSL:1	c.560C>G	p.Thr187Ser	missense	Exon 4 of 16	ENSP00000298281.4	O94913
	PCF11	ENST00000530304.5	TSL:1	c.560C>G	p.Thr187Ser	missense	Exon 4 of 8	ENSP00000431567.1	E9PKN0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0082	T
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.70	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.46	N
PhyloP100		5.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.65	N
REVEL	Benign	0.088
Sift	Benign	0.17	T
Sift4G	Benign	0.59	T
Polyphen		0.012	B
Vest4		0.13
MutPred		0.12		Gain of phosphorylation at T187 (P = 0.0604)
MVP		0.28
MPC		0.17
ClinPred		0.37	T
GERP RS		5.6
Varity_R		0.12
gMVP		0.29
Mutation Taster		=100/0	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: chr11-82875301;