dbSNP rs2070540102: CLASP1:p.Pro1224Leu (chr2-121377533-G-A) – 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_001395891.1(CLASP1):c.3671C>T(p.Pro1224Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,238 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P1224Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CLASP1
NM_001395891.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Publications

0 publications found

Variant links:

Genes affected

CLASP1 (HGNC:17088): (cytoplasmic linker associated protein 1) CLASPs, such as CLASP1, are nonmotor microtubule-associated proteins that interact with CLIPs (e.g., CLIP170; MIM 179838). CLASP1 is involved in the regulation of microtubule dynamics at the kinetochore and throughout the spindle (Maiato et al., 2003 [PubMed 12837247]).[supplied by OMIM, Mar 2008]

CLASP1 Gene-Disease associations (from GenCC):

focal epilepsy
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
complex neurodevelopmental disorder
Inheritance: AD Classification: NO_KNOWN Submitted by: Illumina

CLASP1 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_001395891.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLASP1	NM_001395891.1	MANE Select	c.3671C>T	p.Pro1224Leu	missense	Exon 35 of 41	NP_001382820.1	A0A8V8TLP7
CLASP1	NM_015282.3		c.3608C>T	p.Pro1203Leu	missense	Exon 34 of 40	NP_056097.1	Q7Z460-1
CLASP1	NM_001378003.1		c.3512C>T	p.Pro1171Leu	missense	Exon 33 of 39	NP_001364932.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CLASP1	ENST00000696935.1	MANE Select	c.3671C>T	p.Pro1224Leu	missense	Exon 35 of 41	ENSP00000512981.1	A0A8V8TLP7
CLASP1	ENST00000263710.8	TSL:5	c.3608C>T	p.Pro1203Leu	missense	Exon 34 of 40	ENSP00000263710.4	Q7Z460-1
CLASP1	ENST00000961911.1		c.3551C>T	p.Pro1184Leu	missense	Exon 34 of 40	ENSP00000631970.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1452238

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721424

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33404

American (AMR)

AF:

0.00

AC:

AN:

43598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25886

East Asian (EAS)

AF:

0.00

AC:

AN:

39544

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84528

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52870

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106640

Other (OTH)

AF:

0.00

AC:

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.29

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.3

PhyloP100

PrimateAI

Pathogenic

0.80

PROVEAN

Pathogenic

-5.7

REVEL

Uncertain

0.45

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.83

MutPred

0.30

Gain of helix (P = 0.0425)

MVP

0.65

MPC

1.2

ClinPred

0.99

GERP RS

5.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.30

gMVP

0.49

Mutation Taster

=61/39

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over