Variant 2-218404412-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_021198.3(CTDSP1):c.773G>A(p.Arg258Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000372 in 1,613,968 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 6 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 1 hom. )

Consequence

CTDSP1
NM_021198.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

CTDSP1 (HGNC:21614): (CTD small phosphatase 1) This gene encodes a member of the small C-terminal domain phosphatase (SCP) family of nuclear phosphatases. These proteins play a role in transcriptional regulation through specific dephosphorylation of phosphoserine 5 within tandem heptapeptide repeats of the C-terminal domain of RNA polymerase II. The encoded protein plays a role in neuronal gene silencing in non-neuronal cells, and may also inhibit osteoblast differentiation. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

CTDSP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035119653).

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTDSP1	NM_021198.3 linkuse as main transcript	c.773G>A	p.Arg258Gln	missense_variant	7/7	ENST00000273062.7	NP_067021.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTDSP1	ENST00000273062.7 linkuse as main transcript	c.773G>A	p.Arg258Gln	missense_variant	7/7	1	NM_021198.3	ENSP00000273062	P3	Q9GZU7-1

Frequencies

GnomAD3 genomes

AF:

0.000907

AC:

138

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000251

AC:

AN:

251208

Hom.:

AF XY:

0.000221

AC XY:

AN XY:

135752

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000493

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000317

AC:

463

AN:

1461736

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

208

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.000385

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000907

AC:

138

AN:

152232

Hom.:

Cov.:

AF XY:

0.000766

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000343

Hom.:

Bravo

AF:

0.00117

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000395

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 04, 2023

The c.773G>A (p.R258Q) alteration is located in exon 7 (coding exon 7) of the CTDSP1 gene. This alteration results from a G to A substitution at nucleotide position 773, causing the arginine (R) at amino acid position 258 to be replaced by a glutamine (Q). 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

0.098

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

.;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.86

D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.16

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.041

D;D

Polyphen

0.99

.;D

Vest4

0.21

MVP

0.33

MPC

1.2

ClinPred

0.12

GERP RS

5.3

Varity_R

0.11

gMVP

0.90

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

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