20-56399331-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001324.3(CSTF1):​c.1010C>T​(p.Thr337Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,432 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

CSTF1
NM_001324.3 missense

Scores

6
10
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.56
Variant links:
Genes affected
CSTF1 (HGNC:2483): (cleavage stimulation factor subunit 1) This gene encodes one of three subunits which combine to form cleavage stimulation factor (CSTF). CSTF is involved in the polyadenylation and 3'end cleavage of pre-mRNAs. Similar to mammalian G protein beta subunits, this protein contains transducin-like repeats. Several transcript variants with different 5' UTR, but encoding the same protein, have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CSTF1NM_001324.3 linkc.1010C>T p.Thr337Met missense_variant Exon 5 of 6 ENST00000217109.9 NP_001315.1 Q05048
CSTF1NM_001033521.2 linkc.1010C>T p.Thr337Met missense_variant Exon 5 of 6 NP_001028693.1 Q05048
CSTF1NM_001033522.2 linkc.1010C>T p.Thr337Met missense_variant Exon 5 of 6 NP_001028694.1 Q05048
CSTF1XM_011528600.2 linkc.1010C>T p.Thr337Met missense_variant Exon 5 of 6 XP_011526902.1 Q05048

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CSTF1ENST00000217109.9 linkc.1010C>T p.Thr337Met missense_variant Exon 5 of 6 1 NM_001324.3 ENSP00000217109.4 Q05048

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000479
AC:
7
AN:
1460432
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
726386
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:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

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

The c.1010C>T (p.T337M) alteration is located in exon 5 (coding exon 4) of the CSTF1 gene. This alteration results from a C to T substitution at nucleotide position 1010, causing the threonine (T) at amino acid position 337 to be replaced by a methionine (M). 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
0.35
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.14
T;T;T
Eigen
Pathogenic
0.89
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
.;D;D
M_CAP
Uncertain
0.15
D
MetaRNN
Uncertain
0.73
D;D;D
MetaSVM
Uncertain
0.51
D
MutationAssessor
Benign
1.6
.;L;.
PrimateAI
Pathogenic
0.89
D
PROVEAN
Uncertain
-4.0
D;D;D
REVEL
Uncertain
0.62
Sift
Uncertain
0.020
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
1.0
.;D;.
Vest4
0.70
MutPred
0.46
Gain of MoRF binding (P = 0.0685);Gain of MoRF binding (P = 0.0685);Gain of MoRF binding (P = 0.0685);
MVP
0.72
MPC
2.2
ClinPred
0.99
D
GERP RS
5.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.45
gMVP
0.52

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.17
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: rs1978354659; hg19: chr20-54974387; COSMIC: COSV53860670; COSMIC: COSV53860670; API