Variant rs35490896 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_022111.4(CLSPN):c.3839C>T(p.Ser1280Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.06 in 1,613,982 control chromosomes in the GnomAD database, including 3,175 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.064 ( 368 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2807 hom. )

Consequence

CLSPN
NM_022111.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.43

Variant links:

Genes affected

CLSPN (HGNC:19715): (claspin) The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. The protein is also required for efficient DNA replication during a normal S phase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

CLSPN links:

CLSPN (HGNC:):

CLSPN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017231405).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLSPN	NM_022111.4 linkuse as main transcript	c.3839C>T	p.Ser1280Leu	missense_variant	24/25	ENST00000318121.8	NP_071394.2	Q9HAW4-1
CLSPN	NM_001330490.2 linkuse as main transcript	c.3839C>T	p.Ser1280Leu	missense_variant	24/25		NP_001317419.1	Q9HAW4-3
CLSPN	NM_001190481.2 linkuse as main transcript	c.3647C>T	p.Ser1216Leu	missense_variant	23/24		NP_001177410.1	Q9HAW4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLSPN	ENST00000318121.8 linkuse as main transcript	c.3839C>T	p.Ser1280Leu	missense_variant	24/25	1	NM_022111.4	ENSP00000312995.3		Q9HAW4-1

Frequencies

GnomAD3 genomes

AF:

0.0642

AC:

9764

AN:

152118

Hom.:

369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0856

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0477

Gnomad ASJ

AF:

0.0939

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0653

Gnomad FIN

AF:

0.0464

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0618

Gnomad OTH

AF:

0.0635

GnomAD3 exomes

AF:

0.0553

AC:

13892

AN:

251364

Hom.:

443

AF XY:

0.0567

AC XY:

7697

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.0885

Gnomad AMR exome

AF:

0.0350

Gnomad ASJ exome

AF:

0.0872

Gnomad EAS exome

AF:

0.000598

Gnomad SAS exome

AF:

0.0669

Gnomad FIN exome

AF:

0.0462

Gnomad NFE exome

AF:

0.0611

Gnomad OTH exome

AF:

0.0585

GnomAD4 exome

AF:

0.0595

AC:

87005

AN:

1461746

Hom.:

2807

Cov.:

AF XY:

0.0600

AC XY:

43646

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.0860

Gnomad4 AMR exome

AF:

0.0362

Gnomad4 ASJ exome

AF:

0.0894

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0683

Gnomad4 FIN exome

AF:

0.0455

Gnomad4 NFE exome

AF:

0.0608

Gnomad4 OTH exome

AF:

0.0626

GnomAD4 genome

AF:

0.0643

AC:

9782

AN:

152236

Hom.:

368

Cov.:

AF XY:

0.0634

AC XY:

4723

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0857

Gnomad4 AMR

AF:

0.0477

Gnomad4 ASJ

AF:

0.0939

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0660

Gnomad4 FIN

AF:

0.0464

Gnomad4 NFE

AF:

0.0617

Gnomad4 OTH

AF:

0.0629

Alfa

AF:

0.0618

Hom.:

498

Bravo

AF:

0.0660

TwinsUK

AF:

0.0636

AC:

236

ALSPAC

AF:

0.0550

AC:

212

ESP6500AA

AF:

0.0822

AC:

362

ESP6500EA

AF:

0.0649

AC:

558

ExAC

AF:

0.0563

AC:

6830

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.0693

EpiControl

AF:

0.0639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

.;T;.;.

Eigen

Benign

-0.11

Eigen_PC

Benign

0.064

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.89

D;D;D;D

MetaRNN

Benign

0.0017

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

2.0

M;M;.;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.0

D;D;D;D

REVEL

Benign

0.086

Sift

Benign

0.043

D;D;D;D

Sift4G

Uncertain

0.054

T;T;T;T

Polyphen

0.0040, 0.0070

.;B;B;.

Vest4

0.088

MPC

0.090

ClinPred

0.030

GERP RS

4.3

Varity_R

0.16

gMVP

0.50

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over