X-100824151-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001325.3(CSTF2):c.596C>T(p.Thr199Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,210,327 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T199A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000036 ( 0 hom. 0 hem. )

Consequence

CSTF2
NM_001325.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.19

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26929933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CSTF2	NM_001325.3 link	c.596C>T	p.Thr199Met	missense_variant	Exon 6 of 14	ENST00000372972.7	NP_001316.1	P33240-1
CSTF2	NM_001306206.2 link	c.596C>T	p.Thr199Met	missense_variant	Exon 6 of 15		NP_001293135.1	E7EWR4B3V096B4DUD5
CSTF2	NM_001306209.2 link	c.596C>T	p.Thr199Met	missense_variant	Exon 6 of 14		NP_001293138.1	P33240-2B4DUD5
CSTF2	XM_047441854.1 link	c.596C>T	p.Thr199Met	missense_variant	Exon 6 of 10		XP_047297810.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CSTF2	ENST00000372972.7 link	c.596C>T	p.Thr199Met	missense_variant	Exon 6 of 14	1	NM_001325.3	ENSP00000362063.2	P33240-1
CSTF2	ENST00000415585.7 link	c.596C>T	p.Thr199Met	missense_variant	Exon 6 of 15	1		ENSP00000387996.2	E7EWR4
CSTF2	ENST00000413437.1 link	c.569C>T	p.Thr190Met	missense_variant	Exon 6 of 6	5		ENSP00000415705.1	A0A0A0MT56
CSTF2	ENST00000475126.5 link	n.596C>T		non_coding_transcript_exon_variant	Exon 6 of 14	5		ENSP00000432060.1	E9PID8

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34506

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD3 exomes

AF:

0.0000219

AC:

AN:

182981

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67435

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000217

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000364

AC:

AN:

1097979

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

363345

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112348

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34506

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.596C>T (p.T199M) alteration is located in exon 6 (coding exon 6) of the CSTF2 gene. This alteration results from a C to T substitution at nucleotide position 596, causing the threonine (T) at amino acid position 199 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

Benign

0.15

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.68

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

.;T;T

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.27

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

.;L;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.7

N;N;N

REVEL

Benign

0.096

Sift

Uncertain

0.0030

D;D;D

Sift4G

Uncertain

0.019

D;D;D

Polyphen

0.15

B;B;.

Vest4

0.21

MutPred

0.36

Loss of glycosylation at T199 (P = 0.0408);Loss of glycosylation at T199 (P = 0.0408);.;

MVP

0.63

MPC

1.4

ClinPred

0.37

GERP RS

5.6

Varity_R

0.42

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over