2-121365227-T-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2 BP4_Moderate

The NM_001395891.1(CLASP1):c.4007A>G(p.Asn1336Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,478 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CLASP1 NM_001395891.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94

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 Likely_benign. Variant got -1 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CLASP1
• BP4: Computational evidence support a benign effect (MetaRNN=0.17347631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLASP1	NM_001395891.1	c.4007A>G	p.Asn1336Ser	missense_variant	37/41	ENST00000696935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLASP1	ENST00000696935.1	c.4007A>G	p.Asn1336Ser	missense_variant	37/41		NM_001395891.1	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000804 AC: 2 AN: 248616 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 134908

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000581

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461478 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727010

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2024

The c.3944A>G (p.N1315S) alteration is located in exon 36 (coding exon 35) of the CLASP1 gene. This alteration results from a A to G substitution at nucleotide position 3944, causing the asparagine (N) at amino acid position 1315 to be replaced by a serine (S). 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	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.42
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.081	T;.;.;T;.;.
Eigen	Benign	-0.040
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.17	T;T;T;T;T;T
MetaSVM	Benign	-0.85	T
MutationAssessor	Benign	1.3	L;.;.;L;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D
PrimateAI	Uncertain	0.70	T
Polyphen		0.33	B;.;.;B;.;.
Vest4		0.41, 0.36, 0.33, 0.37, 0.41
MutPred		0.26		Gain of phosphorylation at N1315 (P = 0.021);.;.;Gain of phosphorylation at N1315 (P = 0.021);.;.;
MVP		0.60
MPC		0.47
ClinPred		0.22	T
GERP RS		5.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs1344204517; hg19: chr2-122122803;