Variant 19-7606570-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020902.2(CAMSAP3):c.620C>T(p.Ser207Leu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,375,708 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CAMSAP3
NM_020902.2 missense, splice_region

Scores

Splicing: ADA: 0.01587

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

CAMSAP3 (HGNC:29307): (calmodulin regulated spectrin associated protein family member 3) Enables actin filament binding activity and microtubule minus-end binding activity. Involved in several processes, including microtubule cytoskeleton organization; regulation of organelle organization; and zonula adherens maintenance. Located in cytoplasm; nucleoplasm; and zonula adherens. Colocalizes with centrosome and microtubule minus-end. [provided by Alliance of Genome Resources, Apr 2022]

CAMSAP3 links:

Genome browser will be placed here

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/exons	MANE	Protein	UniProt
CAMSAP3	NM_020902.2 link	c.620C>T	p.Ser207Leu	missense_variant, splice_region_variant	4/17	ENST00000160298.9	NP_065953.1	Q9P1Y5-1
CAMSAP3	NM_001080429.3 link	c.620C>T	p.Ser207Leu	missense_variant, splice_region_variant	4/19		NP_001073898.1	Q9P1Y5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMSAP3	ENST00000160298.9 link	c.620C>T	p.Ser207Leu	missense_variant, splice_region_variant	4/17	2	NM_020902.2	ENSP00000160298.3		Q9P1Y5-1
CAMSAP3	ENST00000446248.4 link	c.620C>T	p.Ser207Leu	missense_variant, splice_region_variant	4/19	1		ENSP00000416797.1		Q9P1Y5-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152160

Hom.:

Cov.:

FAILED QC

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:

0.00

GnomAD3 exomes

AF:

0.0000147

AC:

AN:

135754

Hom.:

AF XY:

0.0000137

AC XY:

AN XY:

72848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000418

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000473

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1375708

Hom.:

Cov.:

AF XY:

0.00000147

AC XY:

AN XY:

678034

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000256

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152160

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74332

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:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 31, 2023

The c.620C>T (p.S207L) alteration is located in exon 4 (coding exon 4) of the CAMSAP3 gene. This alteration results from a C to T substitution at nucleotide position 620, causing the serine (S) at amino acid position 207 to be replaced by a leucine (L). 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

0.38

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0083

T;.

Eigen

Benign

0.016

Eigen_PC

Benign

-0.0057

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.43

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-0.66

N;N

REVEL

Benign

0.14

Sift

Benign

0.40

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.98

D;D

Vest4

0.62

MutPred

0.26

Loss of glycosylation at S207 (P = 0.0219);Loss of glycosylation at S207 (P = 0.0219);

MVP

0.27

MPC

1.4

ClinPred

0.64

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.053

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.016

dbscSNV1_RF

Benign

0.088

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