Variant 17-73260957-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001129885.1(CPSF4L):c.130T>G(p.Phe44Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000316 in 1,550,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CPSF4L
NM_001129885.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.34

Variant links:

Genes affected

CPSF4L (HGNC:33632): (cleavage and polyadenylation specific factor 4 like) Predicted to enable RNA binding activity and metal ion binding activity. Predicted to be involved in pre-mRNA cleavage required for polyadenylation. Predicted to be part of mRNA cleavage and polyadenylation specificity factor complex. [provided by Alliance of Genome Resources, Apr 2022]

CPSF4L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.9

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CPSF4L	NM_001129885.1 linkuse as main transcript	c.130T>G	p.Phe44Val	missense_variant	2/6	ENST00000344935.8
CPSF4L	XM_011525115.3 linkuse as main transcript	c.196T>G	p.Phe66Val	missense_variant	2/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CPSF4L	ENST00000344935.8 linkuse as main transcript	c.130T>G	p.Phe44Val	missense_variant	2/6	1	NM_001129885.1	P1
CPSF4L	ENST00000397671.1 linkuse as main transcript	c.-63T>G		5_prime_UTR_variant	2/7	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000649

AC:

AN:

154178

Hom.:

AF XY:

0.0000122

AC XY:

AN XY:

81800

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:

0.0000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1398360

Hom.:

Cov.:

AF XY:

0.0000261

AC XY:

AN XY:

689690

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:

0.0000204

Gnomad4 NFE exome

AF:

0.0000408

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000389

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

The c.130T>G (p.F44V) alteration is located in exon 2 (coding exon 2) of the CPSF4L gene. This alteration results from a T to G substitution at nucleotide position 130, causing the phenylalanine (F) at amino acid position 44 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.32

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.90

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.8

MutationTaster

Benign

0.80

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-5.3

REVEL

Benign

0.26

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.019

Polyphen

0.86

Vest4

0.69

MutPred

0.72

Loss of stability (P = 0.0491);

MVP

0.081

ClinPred

0.99

GERP RS

1.9

Varity_R

0.33

gMVP

0.81

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over