Genetic Variant CAMSAP1:p.Tyr1529Cys (chr9-135811532-T-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015447.4(CAMSAP1):c.4586A>G(p.Tyr1529Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,607,198 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

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: 3.92

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMSAP1	NM_015447.4 link	c.4586A>G	p.Tyr1529Cys	missense_variant	Exon 17 of 17	ENST00000389532.9	NP_056262.3	Q5T5Y3-1A0A384NY94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMSAP1	ENST00000389532.9 link	c.4586A>G	p.Tyr1529Cys	missense_variant	Exon 17 of 17	5	NM_015447.4	ENSP00000374183.4		Q5T5Y3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000478

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454986

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723054

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00000657

AC:

AN:

152212

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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:

0.000478

Bravo

AF:

0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Feb 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4586A>G (p.Y1529C) alteration is located in exon 17 (coding exon 17) of the CAMSAP1 gene. This alteration results from a A to G substitution at nucleotide position 4586, causing the tyrosine (Y) at amino acid position 1529 to be replaced by a cysteine (C). 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

0.34

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.39

T;.;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Benign

0.037

MetaRNN

Uncertain

0.69

D;D;D

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.;.

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-7.3

D;D;D

REVEL

Uncertain

0.30

Sift

Uncertain

0.021

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.044

B;.;B

Vest4

0.76

MutPred

0.69

Loss of stability (P = 0.0439);.;.;

MVP

0.40

MPC

1.0

ClinPred

0.98

GERP RS

5.2

Varity_R

0.78

gMVP

0.82

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