Variant 2-121377533-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_001395891.1(CLASP1):c.3671C>A(p.Pro1224Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,996 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CLASP1
NM_001395891.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), CLASP1. . Gene score misZ 3.6133 (greater than the threshold 3.09). GenCC has associacion of gene with complex neurodevelopmental disorder.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLASP1	NM_001395891.1 linkuse as main transcript	c.3671C>A	p.Pro1224Gln	missense_variant	35/41	ENST00000696935.1	NP_001382820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLASP1	ENST00000696935.1 linkuse as main transcript	c.3671C>A	p.Pro1224Gln	missense_variant	35/41		NM_001395891.1	ENSP00000512981	A2

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1452236

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721424

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

AF:

0.00000658

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74228

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Feb 12, 2024

The c.3608C>A (p.P1203Q) alteration is located in exon 34 (coding exon 33) of the CLASP1 gene. This alteration results from a C to A substitution at nucleotide position 3608, causing the proline (P) at amino acid position 1203 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

Uncertain

0.45

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;.;.;T;.;.

Eigen

Pathogenic

0.83

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

.;D;D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.63

D;D;D;D;D;D

MetaSVM

Benign

-0.56

MutationAssessor

Uncertain

2.3

M;.;.;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.9

.;D;.;D;D;.

REVEL

Uncertain

0.41

Sift

Uncertain

0.0020

.;D;.;D;D;.

Sift4G

Uncertain

0.016

.;D;D;D;D;D

Polyphen

1.0

D;.;.;D;.;.

Vest4

0.72, 0.67, 0.68, 0.79

MutPred

0.28

Gain of helix (P = 0.0854);.;.;Gain of helix (P = 0.0854);.;.;

MVP

0.54

MPC

1.2

ClinPred

0.98

GERP RS

5.8

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.31

gMVP

0.52

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