chrX-100822260-C-T

Variant names:

• chrX-100822260-C-T
• rs766161610
• NM_001325.3:c.147C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001325.3(CSTF2):​c.147C>T​(p.Tyr49Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000249 in 1,207,129 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000045 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000023 (0 hom. 8 hem.)
• Consequence: CSTF2 NM_001325.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

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]

CSTF2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder, X-linked 113

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant X-100822260-C-T is Benign according to our data. Variant chrX-100822260-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 745214.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.9 with no splicing effect.
• BS2: High Hemizygotes in GnomAdExome4 at 8 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001325.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTF2	NM_001325.3	MANE Select	c.147C>T	p.Tyr49Tyr	synonymous	Exon 3 of 14	NP_001316.1	P33240-1
	CSTF2	NM_001306206.2		c.147C>T	p.Tyr49Tyr	synonymous	Exon 3 of 15	NP_001293135.1	E7EWR4
	CSTF2	NM_001306209.2		c.147C>T	p.Tyr49Tyr	synonymous	Exon 3 of 14	NP_001293138.1	P33240-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSTF2	ENST00000372972.7	TSL:1 MANE Select	c.147C>T	p.Tyr49Tyr	synonymous	Exon 3 of 14	ENSP00000362063.2	P33240-1
	CSTF2	ENST00000415585.7	TSL:1	c.147C>T	p.Tyr49Tyr	synonymous	Exon 3 of 15	ENSP00000387996.2	E7EWR4
	CSTF2	ENST00000866722.1		c.147C>T	p.Tyr49Tyr	synonymous	Exon 3 of 16	ENSP00000536781.1

Frequencies

GnomAD3 genomes AF: 0.0000449 AC: 5 AN: 111441 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000980

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000951

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000165 AC: 3 AN: 181447 AF XY: 0.0000152

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000735

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000123

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000228 AC: 25 AN: 1095688 Hom.: 0 Cov.: 29 AF XY: 0.0000222 AC XY: 8 AN XY: 361138

African (AFR) AF: 0.0000380 AC: 1 AN: 26350

American (AMR) AF: 0.0000569 AC: 2 AN: 35128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19321

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30191

South Asian (SAS) AF: 0.00 AC: 0 AN: 53857

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40502

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.0000214 AC: 18 AN: 840207

Other (OTH) AF: 0.0000652 AC: 3 AN: 46016

GnomAD4 genome AF: 0.0000449 AC: 5 AN: 111441 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33641

African (AFR) AF: 0.0000980 AC: 3 AN: 30610

American (AMR) AF: 0.0000951 AC: 1 AN: 10515

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3579

South Asian (SAS) AF: 0.00 AC: 0 AN: 2635

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5914

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53117

Other (OTH) AF: 0.00 AC: 0 AN: 1509

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.6
DANN	Benign	0.71
PhyloP100		1.9
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs766161610; hg19: chrX-100077249; COSMIC: COSV63376249; COSMIC: COSV63376249;