X-100820441-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_001325.3(CSTF2):​c.25C>T​(p.Pro9Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,210,643 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)
Exomes 𝑓: 0.000011 ( 0 hom. 7 hem. )

Consequence

CSTF2
NM_001325.3 missense

Scores

2
8
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.81
Variant links:
Genes affected
CSTF2 (HGNC:2484): (cleavage stimulation factor subunit 2) This gene encodes a nuclear protein with an RRM (RNA recognition motif) domain. The protein is a member of the cleavage stimulation factor (CSTF) complex that is involved in the 3' end cleavage and polyadenylation of pre-mRNAs. Specifically, this protein binds GU-rich elements within the 3'-untranslated region of mRNAs. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.3276945).
BS2
High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSTF2NM_001325.3 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 14 ENST00000372972.7 NP_001316.1 P33240-1
CSTF2NM_001306206.2 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 15 NP_001293135.1 E7EWR4B3V096B4DUD5
CSTF2NM_001306209.2 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 14 NP_001293138.1 P33240-2B4DUD5
CSTF2XM_047441854.1 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 10 XP_047297810.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSTF2ENST00000372972.7 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 14 1 NM_001325.3 ENSP00000362063.2 P33240-1
CSTF2ENST00000415585.7 linkc.25C>T p.Pro9Ser missense_variant Exon 1 of 15 1 ENSP00000387996.2 E7EWR4
CSTF2ENST00000475126.5 linkn.25C>T non_coding_transcript_exon_variant Exon 1 of 14 5 ENSP00000432060.1 E9PID8
CSTF2ENST00000413437.1 linkc.-177C>T upstream_gene_variant 5 ENSP00000415705.1 A0A0A0MT56

Frequencies

GnomAD3 genomes
AF:
0.00000888
AC:
1
AN:
112656
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34836
show subpopulations
Gnomad AFR
AF:
0.0000322
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000109
AC:
12
AN:
1097987
Hom.:
0
Cov.:
30
AF XY:
0.0000193
AC XY:
7
AN XY:
363341
show subpopulations
Gnomad4 AFR exome
AF:
0.0000379
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:
0.0000119
Gnomad4 OTH exome
AF:
0.0000217
GnomAD4 genome
AF:
0.00000888
AC:
1
AN:
112656
Hom.:
0
Cov.:
24
AF XY:
0.00
AC XY:
0
AN XY:
34836
show subpopulations
Gnomad4 AFR
AF:
0.0000322
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.25C>T (p.P9S) alteration is located in exon 1 (coding exon 1) of the CSTF2 gene. This alteration results from a C to T substitution at nucleotide position 25, causing the proline (P) at amino acid position 9 to be replaced by a serine (S). 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
Uncertain
0.50
BayesDel_addAF
Uncertain
0.026
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.16
.;T
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Pathogenic
0.66
D
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-0.43
T
MutationAssessor
Benign
0.40
.;N
PrimateAI
Uncertain
0.73
T
PROVEAN
Uncertain
-2.5
N;N
REVEL
Uncertain
0.30
Sift
Uncertain
0.0080
D;D
Sift4G
Benign
0.14
T;T
Polyphen
0.67
P;B
Vest4
0.32
MutPred
0.47
Gain of phosphorylation at P9 (P = 0.06);Gain of phosphorylation at P9 (P = 0.06);
MVP
0.93
MPC
1.9
ClinPred
0.93
D
GERP RS
4.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.61
gMVP
0.80

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

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

Other links and lift over

dbSNP: rs1242418398; hg19: chrX-100075430; API