Genetic Variant NM_001142565.3:c.167G>T (chr11-61421496-C-A) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001142565.3(CPSF7):c.167G>T(p.Arg56Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CPSF7
NM_001142565.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.63

Variant links:

Genes affected

CPSF7 (HGNC:30098): (cleavage and polyadenylation specific factor 7) Cleavage factor Im (CFIm) is one of six factors necessary for correct cleavage and polyadenylation of pre-mRNAs. CFIm is composed of three different subunits of 25, 59, and 68 kDa, and it functions as a heterotetramer, with a dimer of the 25 kDa subunit binding to two of the 59 or 68 kDa subunits. The protein encoded by this gene represents the 59 kDa subunit, which can interact with the splicing factor U2 snRNP Auxiliary Factor (U2AF) 65 to link the splicing and polyadenylation complexes. [provided by RefSeq, Oct 2016]

CPSF7 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CPSF7	NM_001142565.3 link	c.167G>T	p.Arg56Leu	missense_variant	Exon 3 of 10	ENST00000439958.8	NP_001136037.1	Q8N684-2B4DGF8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CPSF7	ENST00000439958.8 link	c.167G>T	p.Arg56Leu	missense_variant	Exon 3 of 10	1	NM_001142565.3	ENSP00000397203.3		Q8N684-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251452

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135902

show subpopulations

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:

0.0000264

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461798

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.00000525

Hom.:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.049

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

.;T;.;.;T;.;T;T;T;.;.;T;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.85

D;D;.;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.0094

MetaRNN

Benign

0.21

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

.;L;L;L;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.4

N;N;N;N;N;N;N;N;N;N;N;N;.

REVEL

Benign

0.080

Sift

Benign

0.26

T;T;T;T;T;T;T;T;T;T;T;T;.

Sift4G

Benign

0.30

T;T;T;T;.;T;.;.;T;.;.;.;T

Polyphen

0.98

D;B;D;D;.;.;.;.;D;.;.;.;.

Vest4

0.36

MutPred

0.22

.;Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);Gain of catalytic residue at R56 (P = 0.0814);

MVP

0.51

MPC

0.94

ClinPred

0.46

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.55

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.55

Position offset: -5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over