20-56399331-C-T

Variant names:

• chr20-56399331-C-T
• rs1978354659
• NM_001324.3:c.1010C>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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.56

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]

ACMG classification

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
CSTF1	NM_001324.3	c.1010C>T	p.Thr337Met	missense_variant	Exon 5 of 6	ENST00000217109.9	NP_001315.1
CSTF1	NM_001033521.2	c.1010C>T	p.Thr337Met	missense_variant	Exon 5 of 6		NP_001028693.1
CSTF1	NM_001033522.2	c.1010C>T	p.Thr337Met	missense_variant	Exon 5 of 6		NP_001028694.1
CSTF1	XM_011528600.2	c.1010C>T	p.Thr337Met	missense_variant	Exon 5 of 6		XP_011526902.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTF1	ENST00000217109.9	c.1010C>T	p.Thr337Met	missense_variant	Exon 5 of 6	1	NM_001324.3	ENSP00000217109.4

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

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

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

Other links and lift over

dbSNP: rs1978354659; hg19: chr20-54974387; COSMIC: COSV53860670; COSMIC: COSV53860670;