Genetic Variant CLSPN:p.Met1207Val (chr1-35738037-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_022111.4(CLSPN):c.3619A>G(p.Met1207Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000015 in 1,335,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

CLSPN
NM_022111.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.61

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022111.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLSPN	NM_022111.4	MANE Select	c.3619A>G	p.Met1207Val	missense	Exon 22 of 25	NP_071394.2
CLSPN	NM_001330490.2		c.3619A>G	p.Met1207Val	missense	Exon 22 of 25	NP_001317419.1	Q9HAW4-3
CLSPN	NM_001190481.2		c.3427A>G	p.Met1143Val	missense	Exon 21 of 24	NP_001177410.1	Q9HAW4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLSPN	ENST00000318121.8	TSL:1 MANE Select	c.3619A>G	p.Met1207Val	missense	Exon 22 of 25	ENSP00000312995.3	Q9HAW4-1
CLSPN	ENST00000251195.9	TSL:1	c.3619A>G	p.Met1207Val	missense	Exon 22 of 25	ENSP00000251195.5	Q9HAW4-3
CLSPN	ENST00000520551.1	TSL:1	c.3460A>G	p.Met1154Val	missense	Exon 22 of 25	ENSP00000428848.1	E7ESG2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000484

AC:

AN:

206686

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000734

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000150

AC:

AN:

1335644

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

660676

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30200

American (AMR)

AF:

0.00

AC:

AN:

37714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22994

East Asian (EAS)

AF:

0.0000279

AC:

AN:

35834

South Asian (SAS)

AF:

0.00

AC:

AN:

61518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47788

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5340

European-Non Finnish (NFE)

AF:

9.61e-7

AC:

AN:

1040128

Other (OTH)

AF:

0.00

AC:

AN:

54128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.043

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

PhyloP100

4.6

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

REVEL

Benign

0.19

Sift

Uncertain

0.028

Sift4G

Benign

0.10

Polyphen

0.99

Vest4

0.77

MutPred

0.31

Loss of disorder (P = 0.0619)

MVP

0.47

MPC

0.41

ClinPred

0.67

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.39

Mutation Taster

=75/25

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over