X-100832804-C-T

Variant names:

• chrX-100832804-C-T
• NM_001325.3:c.1102C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001325.3(CSTF2):​c.1102C>T​(p.Pro368Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,100 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. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: CSTF2 NM_001325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.84

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]

ACMG classification

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=0.14747968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2	NM_001325.3	c.1102C>T	p.Pro368Ser	missense_variant	Exon 10 of 14	ENST00000372972.7	NP_001316.1
CSTF2	NM_001306206.2	c.1162C>T	p.Pro388Ser	missense_variant	Exon 11 of 15		NP_001293135.1
CSTF2	NM_001306209.2	c.1051C>T	p.Pro351Ser	missense_variant	Exon 10 of 14		NP_001293138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTF2	ENST00000372972.7	c.1102C>T	p.Pro368Ser	missense_variant	Exon 10 of 14	1	NM_001325.3	ENSP00000362063.2
CSTF2	ENST00000415585.7	c.1162C>T	p.Pro388Ser	missense_variant	Exon 11 of 15	1		ENSP00000387996.2
CSTF2	ENST00000475126.5	n.1051C>T		non_coding_transcript_exon_variant	Exon 10 of 14	5		ENSP00000432060.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097100 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 362472

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: 0.0000186

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 01, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1102C>T (p.P368S) alteration is located in exon 10 (coding exon 10) of the CSTF2 gene. This alteration results from a C to T substitution at nucleotide position 1102, causing the proline (P) at amino acid position 368 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	Benign	0.060
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.039	.;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.95	N;N
REVEL	Benign	0.10
Sift	Benign	0.78	T;T
Sift4G	Benign	0.25	T;T
Polyphen		0.0090	B;B
Vest4		0.47
MutPred		0.23		Gain of phosphorylation at P388 (P = 0.0033);.;
MVP		0.59
MPC		1.1
ClinPred		0.83	D
GERP RS		5.0
Varity_R		0.33
gMVP		0.83

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100087793;