9-135820901-C-T

Position:

chr9-135820901-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS1

The NM_015447.4(CAMSAP1):c.3760G>A(p.Asp1254Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

CAMSAP1
NM_015447.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

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:

CAMSAP1 (HGNC:):

CAMSAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12425697).

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0000171 (25/1461456) while in subpopulation EAS AF= 0.000453 (18/39700). AF 95% confidence interval is 0.000293. There are 0 homozygotes in gnomad4_exome. There are 10 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMSAP1	NM_015447.4 linkuse as main transcript	c.3760G>A	p.Asp1254Asn	missense_variant	11/17	ENST00000389532.9	NP_056262.3	Q5T5Y3-1A0A384NY94

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CAMSAP1	ENST00000389532.9 linkuse as main transcript	c.3760G>A	p.Asp1254Asn	missense_variant	11/17	5	NM_015447.4	ENSP00000374183.4	Q5T5Y3-1
CAMSAP1	ENST00000312405.10 linkuse as main transcript	c.2926G>A	p.Asp976Asn	missense_variant	9/15	1		ENSP00000312463.6	Q5T5Y3-2
CAMSAP1	ENST00000409386.3 linkuse as main transcript	c.3793G>A	p.Asp1265Asn	missense_variant	12/18	5		ENSP00000386420.3	Q5T5Y3-3
CAMSAP1	ENST00000483991.5 linkuse as main transcript	n.2822G>A		non_coding_transcript_exon_variant	4/11	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

250740

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461456

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727034

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000453

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Dec 04, 2024

The c.3760G>A (p.D1254N) alteration is located in exon 11 (coding exon 11) of the CAMSAP1 gene. This alteration results from a G to A substitution at nucleotide position 3760, causing the aspartic acid (D) at amino acid position 1254 to be replaced by an asparagine (N). 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

0.088

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.063

T;.;.

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.5

M;.;.

PrimateAI

Benign

0.31

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.80

P;.;B

Vest4

0.13

MutPred

0.12

Loss of phosphorylation at S1252 (P = 0.1126);.;.;

MVP

0.24

MPC

0.69

ClinPred

0.21

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.056

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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