NM_001395891.1:c.3868T>C

Variant names:

• chr2-121367669-A-G
• NM_001395891.1:c.3868T>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395891.1(CLASP1):​c.3868T>C​(p.Tyr1290His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLASP1 NM_001395891.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3975385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLASP1	NM_001395891.1	c.3868T>C	p.Tyr1290His	missense_variant	Exon 36 of 41	ENST00000696935.1	NP_001382820.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLASP1	ENST00000696935.1	c.3868T>C	p.Tyr1290His	missense_variant	Exon 36 of 41		NM_001395891.1	ENSP00000512981.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 08, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3805T>C (p.Y1269H) alteration is located in exon 35 (coding exon 34) of the CLASP1 gene. This alteration results from a T to C substitution at nucleotide position 3805, causing the tyrosine (Y) at amino acid position 1269 to be replaced by a histidine (H). 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	0.41
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;.;.;T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Pathogenic	0.99	.;D;D;D;D;D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.40	T;T;T;T;T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.3	M;.;.;M;.;.
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.6	.;D;.;D;D;.
REVEL	Benign	0.26
Sift	Benign	0.041	.;D;.;D;D;.
Sift4G	Uncertain	0.030	.;D;D;D;D;D
Polyphen		0.97	D;.;.;D;.;.
Vest4		0.68, 0.67, 0.63, 0.65, 0.64
MutPred		0.33		Loss of phosphorylation at Y1269 (P = 0.0368);.;.;Loss of phosphorylation at Y1269 (P = 0.0368);.;.;
MVP		0.52
MPC		1.3
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.13
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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.

Other links and lift over

hg19: chr2-122125245;