Genetic Variant CLSPN:p.Glu1195Asp (chr1-35738071-T-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_022111.4(CLSPN):c.3585A>T(p.Glu1195Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLSPN
NM_022111.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 0.421

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12097144).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSPN	NM_022111.4 link	c.3585A>T	p.Glu1195Asp	missense_variant	Exon 22 of 25	ENST00000318121.8	NP_071394.2	Q9HAW4-1
CLSPN	NM_001330490.2 link	c.3585A>T	p.Glu1195Asp	missense_variant	Exon 22 of 25		NP_001317419.1	Q9HAW4-3
CLSPN	NM_001190481.2 link	c.3393A>T	p.Glu1131Asp	missense_variant	Exon 21 of 24		NP_001177410.1	Q9HAW4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSPN	ENST00000318121.8 link	c.3585A>T	p.Glu1195Asp	missense_variant	Exon 22 of 25	1	NM_022111.4	ENSP00000312995.3		Q9HAW4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1286382

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

635168

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myoepithelial tumor

Uncertain:1

Nov 01, 2022

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0061

.;T;.;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.15

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.64

T;T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;.;.

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.94

N;N;N;N

REVEL

Benign

0.079

Sift

Benign

0.036

D;D;T;T

Sift4G

Uncertain

0.042

D;T;D;T

Polyphen

0.037

.;B;B;.

Vest4

0.10

MutPred

0.098

Loss of methylation at K1191 (P = 0.1423);Loss of methylation at K1191 (P = 0.1423);.;.;

MVP

0.36

MPC

0.11

ClinPred

0.19

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.041

gMVP

0.10

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over