Genetic Variant CCSAP:p.Asp195Asn (chr1-229326791-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_145257.5(CCSAP):c.583G>A(p.Asp195Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,614,110 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: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CCSAP
NM_145257.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.05

Variant links:

Genes affected

CCSAP (HGNC:29578): (centriole, cilia and spindle associated protein) Enables microtubule binding activity. Involved in mitotic spindle microtubule depolymerization and regulation of mitotic spindle assembly. Located in axon; ciliary transition zone; and cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

CCSAP links:

Genome browser will be placed here

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=0.24137294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCSAP	NM_145257.5 link	c.583G>A	p.Asp195Asn	missense_variant	Exon 3 of 4	ENST00000284617.7	NP_660300.3	Q6IQ19-1
CCSAP	NM_001410936.1 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 2 of 3		NP_001397865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCSAP	ENST00000284617.7 link	c.583G>A	p.Asp195Asn	missense_variant	Exon 3 of 4	1	NM_145257.5	ENSP00000284617.2	Q6IQ19-1
CCSAP	ENST00000366687.5 link	c.583G>A	p.Asp195Asn	missense_variant	Exon 2 of 3	1		ENSP00000355648.1	Q6IQ19-1
CCSAP	ENST00000483092.1 link	n.1566G>A		non_coding_transcript_exon_variant	Exon 3 of 4	1
CCSAP	ENST00000366686.1 link	c.241G>A	p.Asp81Asn	missense_variant	Exon 2 of 3	2		ENSP00000355647.1	Q6IQ19-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000278

AC:

AN:

251378

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000958

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

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:

152220

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

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

Alfa

AF:

0.0000282

Hom.:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 28, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.583G>A (p.D195N) alteration is located in exon 3 (coding exon 2) of the CCSAP gene. This alteration results from a G to A substitution at nucleotide position 583, causing the aspartic acid (D) at amino acid position 195 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

0.15

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;T;.

Eigen

Benign

0.093

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.88

D;.;T

M_CAP

Benign

0.070

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-0.62

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.26

Sift

Benign

0.041

D;D;D

Sift4G

Benign

0.071

T;T;D

Polyphen

1.0

D;D;.

Vest4

0.20

MutPred

0.39

Gain of MoRF binding (P = 0.0576);Gain of MoRF binding (P = 0.0576);.;

MVP

0.55

MPC

0.80

ClinPred

0.79

GERP RS

4.5

Varity_R

0.30

gMVP

0.13

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