X-100822262-A-C

Variant names:

• chrX-100822262-A-C
• NM_001325.3:c.149A>C

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2 PP3_Strong PP5

The NM_001325.3(CSTF2):​c.149A>C​(p.Asp50Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 22)
• Consequence: CSTF2 NM_001325.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 8.64

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 Likely_pathogenic. Variant got 7 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.984
• PP5: Variant X-100822262-A-C is Pathogenic according to our data. Variant chrX-100822262-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 2692386.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2	NM_001325.3	c.149A>C	p.Asp50Ala	missense_variant	Exon 3 of 14	ENST00000372972.7	NP_001316.1
CSTF2	NM_001306206.2	c.149A>C	p.Asp50Ala	missense_variant	Exon 3 of 15		NP_001293135.1
CSTF2	NM_001306209.2	c.149A>C	p.Asp50Ala	missense_variant	Exon 3 of 14		NP_001293138.1
CSTF2	XM_047441854.1	c.149A>C	p.Asp50Ala	missense_variant	Exon 3 of 10		XP_047297810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CSTF2	ENST00000372972.7	c.149A>C	p.Asp50Ala	missense_variant	Exon 3 of 14	1	NM_001325.3	ENSP00000362063.2
CSTF2	ENST00000415585.7	c.149A>C	p.Asp50Ala	missense_variant	Exon 3 of 15	1		ENSP00000387996.2
CSTF2	ENST00000413437.1	c.122A>C	p.Asp41Ala	missense_variant	Exon 3 of 6	5		ENSP00000415705.1
CSTF2	ENST00000475126.5	n.149A>C		non_coding_transcript_exon_variant	Exon 3 of 14	5		ENSP00000432060.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 22

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Intellectual developmental disorder, X-linked 113 Pathogenic:1

Feb 06, 2024

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	.;T;T
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D
M_CAP	Pathogenic	0.72	D
MetaRNN	Pathogenic	0.98	D;D;D
MetaSVM	Uncertain	0.76	D
MutationAssessor	Pathogenic	3.4	.;M;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-7.6	D;D;D
REVEL	Pathogenic	0.95
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		1.0	D;D;.
Vest4		0.93
MutPred		0.90		Loss of ubiquitination at K55 (P = 0.0537);Loss of ubiquitination at K55 (P = 0.0537);.;
MVP		0.93
MPC		3.4
ClinPred		1.0	D
GERP RS		5.1
Varity_R		0.96
gMVP		0.95

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-100077251;