Variant 9-135818504-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015447.4(CAMSAP1):c.4072C>G(p.Leu1358Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,458,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CAMSAP1
NM_015447.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.77

Variant links:

Genes affected

CAMSAP1 (HGNC:19946): (calmodulin regulated spectrin associated protein 1) Enables microtubule minus-end binding activity and spectrin binding activity. Involved in several processes, including neuron projection development; regulation of cell morphogenesis; and regulation of microtubule polymerization. Located in microtubule. Colocalizes with microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]

CAMSAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.107703775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMSAP1	NM_015447.4 linkuse as main transcript	c.4072C>G	p.Leu1358Val	missense_variant	13/17	ENST00000389532.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMSAP1	ENST00000389532.9 linkuse as main transcript	c.4072C>G	p.Leu1358Val	missense_variant	13/17	5	NM_015447.4	P2	Q5T5Y3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248364

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134626

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

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:

6.85e-7

AC:

AN:

1458952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2024

The c.4072C>G (p.L1358V) alteration is located in exon 13 (coding exon 13) of the CAMSAP1 gene. This alteration results from a C to G substitution at nucleotide position 4072, causing the leucine (L) at amino acid position 1358 to be replaced by a valine (V). 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

0.087

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.028

T;.;.

Eigen

Benign

-0.055

Eigen_PC

Benign

-0.082

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.025

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.0

L;.;.

MutationTaster

Benign

0.56

D;D;D

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.30

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.47

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

1.0

D;.;P

Vest4

0.25

MutPred

0.15

Gain of relative solvent accessibility (P = 0.0166);.;.;

MVP

0.47

MPC

0.99

ClinPred

0.31

GERP RS

3.5

Varity_R

0.034

gMVP

0.41

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