Variant 2-121377584-G-A 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.3620C>T(p.Thr1207Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (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.3620C>T	p.Thr1207Ile	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.3620C>T	p.Thr1207Ile	missense_variant	35/41		NM_001395891.1	ENSP00000512981	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1443002

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716214

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: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 09, 2021

The CLASP1 c.3557C>T (p.Thr1186Ile) variant is a missense variant. A literature search was conducted for the gene, cDNA change, and amino acid change. No publications were identified through this search. The variant is not reported in version 2.1.1 or version 3.1.1 of the Genome Aggregation Database despite its location in a region of good sequencing coverage, which suggests that the variant is rare. Multiple lines of computational evidence predict the variant to have a deleterious impact on the protein, though these predictions have not been confirmed experimentally. Based on the available evidence, the p.Thr1186Ile variant is classified as a variant of uncertain significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;.;.;T;.;.

Eigen

Pathogenic

0.98

Eigen_PC

Pathogenic

0.97

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D;D;D;D

M_CAP

Benign

0.033

MetaRNN

Uncertain

0.69

D;D;D;D;D;D

MetaSVM

Uncertain

0.043

MutationAssessor

Uncertain

2.9

M;.;.;M;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Pathogenic

0.86

PROVEAN

Pathogenic

-5.1

.;D;.;D;D;D

REVEL

Uncertain

0.48

Sift

Pathogenic

0.0

.;D;.;D;D;D

Sift4G

Pathogenic

0.0010

.;D;D;D;D;D

Polyphen

1.0

D;.;.;D;.;.

Vest4

0.85, 0.81, 0.81, 0.85, 0.86

MutPred

0.26

Loss of disorder (P = 0.0639);.;.;Loss of disorder (P = 0.0639);.;.;

MVP

0.71

MPC

1.3

ClinPred

1.0

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.82

gMVP

0.78

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

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