X-100832774-C-T

Variant names:

• chrX-100832774-C-T
• NM_001325.3:c.1072C>T

Variant summary

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

The NM_001325.3(CSTF2):​c.1072C>T​(p.His358Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: CSTF2 NM_001325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.60

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2	NM_001325.3	c.1072C>T	p.His358Tyr	missense_variant	Exon 10 of 14	ENST00000372972.7	NP_001316.1
CSTF2	NM_001306206.2	c.1132C>T	p.His378Tyr	missense_variant	Exon 11 of 15		NP_001293135.1
CSTF2	NM_001306209.2	c.1021C>T	p.His341Tyr	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.1072C>T	p.His358Tyr	missense_variant	Exon 10 of 14	1	NM_001325.3	ENSP00000362063.2
CSTF2	ENST00000415585.7	c.1132C>T	p.His378Tyr	missense_variant	Exon 11 of 15	1		ENSP00000387996.2
CSTF2	ENST00000475126.5	n.1021C>T		non_coding_transcript_exon_variant	Exon 10 of 14	5		ENSP00000432060.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1072C>T (p.H358Y) 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 1072, causing the histidine (H) at amino acid position 358 to be replaced by a tyrosine (Y). 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	0.11
BayesDel_addAF	Benign	-0.032	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.064	.;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	.;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.0	N;N
REVEL	Benign	0.10
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	1.0	T;T
Polyphen		0.98	D;D
Vest4		0.58
MutPred		0.24		Gain of phosphorylation at H378 (P = 0.0067);.;
MVP		0.40
MPC		1.1
ClinPred		0.96	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.44
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-100087763;