NM_017437.3:c.28C>T

Variant names:

• chr14-92131012-C-T
• rs770435353
• NM_017437.3:c.28C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_017437.3(CPSF2):​c.28C>T​(p.Leu10Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CPSF2 NM_017437.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.57

Genes affected

CPSF2 (HGNC:2325): (cleavage and polyadenylation specific factor 2) Predicted to enable RNA binding activity. Involved in mRNA 3'-end processing by stem-loop binding activity and cleavage. Located in membrane. Part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35035723).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF2	NM_017437.3	c.28C>T	p.Leu10Phe	missense_variant	Exon 3 of 16	ENST00000298875.9	NP_059133.1
CPSF2	NM_001322272.2	c.28C>T	p.Leu10Phe	missense_variant	Exon 3 of 16		NP_001309201.1
CPSF2	NM_001322270.2	c.28C>T	p.Leu10Phe	missense_variant	Exon 3 of 15		NP_001309199.1
CPSF2	NM_001322271.2	c.-272C>T		5_prime_UTR_variant	Exon 3 of 15		NP_001309200.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF2	ENST00000298875.9	c.28C>T	p.Leu10Phe	missense_variant	Exon 3 of 16	1	NM_017437.3	ENSP00000298875.4
CPSF2	ENST00000553427.5	c.28C>T	p.Leu10Phe	missense_variant	Exon 3 of 4	4		ENSP00000451418.1
CPSF2	ENST00000554290.1	n.28C>T		non_coding_transcript_exon_variant	Exon 3 of 5	4		ENSP00000452503.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248884 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 134496

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459310 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725864

Gnomad4 AFR exome AF: 0.0000300

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

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.027	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.42	T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.4	N;D
REVEL	Benign	0.23
Sift	Benign	0.21	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.030	B;.
Vest4		0.48
MutPred		0.62		Loss of ubiquitination at K6 (P = 0.0768);Loss of ubiquitination at K6 (P = 0.0768);
MVP		0.81
MPC		0.69
ClinPred		0.80	D
GERP RS		5.7
Varity_R		0.36
gMVP		0.78

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

LitVar

Other links and lift over

dbSNP: rs770435353; hg19: chr14-92597356;