X-100826656-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001325.3(CSTF2):​c.725C>T​(p.Ala242Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000182 in 1,096,990 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000018 ( 0 hom. 0 hem. )

Consequence

CSTF2
NM_001325.3 missense

Scores

1
4
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.57
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.262347).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSTF2NM_001325.3 linkc.725C>T p.Ala242Val missense_variant Exon 7 of 14 ENST00000372972.7 NP_001316.1 P33240-1
CSTF2NM_001306206.2 linkc.725C>T p.Ala242Val missense_variant Exon 7 of 15 NP_001293135.1 E7EWR4B3V096B4DUD5
CSTF2XM_047441854.1 linkc.725C>T p.Ala242Val missense_variant Exon 7 of 10 XP_047297810.1
CSTF2NM_001306209.2 linkc.703-29C>T intron_variant Intron 6 of 13 NP_001293138.1 P33240-2B4DUD5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSTF2ENST00000372972.7 linkc.725C>T p.Ala242Val missense_variant Exon 7 of 14 1 NM_001325.3 ENSP00000362063.2 P33240-1
CSTF2ENST00000415585.7 linkc.725C>T p.Ala242Val missense_variant Exon 7 of 15 1 ENSP00000387996.2 E7EWR4
CSTF2ENST00000475126.5 linkn.703-29C>T intron_variant Intron 6 of 13 5 ENSP00000432060.1 E9PID8

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.0000164
AC:
3
AN:
183185
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67643
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000110
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:
0.00
GnomAD4 exome
AF:
0.00000182
AC:
2
AN:
1096990
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
362492
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000568
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.:
22
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.725C>T (p.A242V) alteration is located in exon 7 (coding exon 7) of the CSTF2 gene. This alteration results from a C to T substitution at nucleotide position 725, causing the alanine (A) at amino acid position 242 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
0.18
BayesDel_addAF
Benign
-0.34
T
BayesDel_noAF
Benign
-0.51
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.050
.;T
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.96
D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.6
.;M
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.30
N;N
REVEL
Benign
0.17
Sift
Benign
0.56
T;T
Sift4G
Benign
0.19
T;T
Polyphen
0.56
P;P
Vest4
0.57
MutPred
0.28
Gain of catalytic residue at A242 (P = 0.0074);Gain of catalytic residue at A242 (P = 0.0074);
MVP
0.75
MPC
1.3
ClinPred
0.40
T
GERP RS
3.6
Varity_R
0.28
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs761627143; hg19: chrX-100081645; API