12-69258811-C-A

Variant names:

• chr12-69258811-C-A
• NM_007007.3:c.916C>A

Variant summary

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

The NM_007007.3(CPSF6):​c.916C>A​(p.Pro306Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CPSF6 NM_007007.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.83

Genes affected

CPSF6 (HGNC:13871): (cleavage and polyadenylation specific factor 6) The protein encoded by this gene is one subunit of a cleavage factor required for 3' RNA cleavage and polyadenylation processing. The interaction of the protein with the RNA is one of the earliest steps in the assembly of the 3' end processing complex and facilitates the recruitment of other processing factors. The cleavage factor complex is composed of four polypeptides. This gene encodes the 68kD subunit. It has a domain organization reminiscent of spliceosomal proteins. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF6	NM_007007.3	c.916C>A	p.Pro306Thr	missense_variant	Exon 6 of 10	ENST00000435070.7	NP_008938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF6	ENST00000435070.7	c.916C>A	p.Pro306Thr	missense_variant	Exon 6 of 10	1	NM_007007.3	ENSP00000391774.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461728 Hom.: 0 Cov.: 35 AF XY: 0.00000138 AC XY: 1 AN XY: 727158

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.41	T;T;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.0074	T
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.40	T
MutationAssessor	Benign	1.9	L;.;.
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-4.2	D;D;D
REVEL	Benign	0.21
Sift	Benign	0.10	T;D;T
Sift4G	Uncertain	0.015	D;D;D
Polyphen		0.95	P;.;D
Vest4		0.61
MutPred		0.40		Gain of phosphorylation at P306 (P = 0.0042);.;.;
MVP		0.50
MPC		1.2
ClinPred		0.95	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.33
gMVP		0.19

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: chr12-69652591;