Variant 1-229326985-T-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_145257.5(CCSAP):c.389A>G(p.Glu130Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000618 in 1,456,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.0000062 ( 0 hom. )

Consequence

CCSAP
NM_145257.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.45

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:

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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=0.13618281).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCSAP	NM_145257.5 linkuse as main transcript	c.389A>G	p.Glu130Gly	missense_variant	3/4	ENST00000284617.7	NP_660300.3
CCSAP	NM_001410936.1 linkuse as main transcript	c.47A>G	p.Glu16Gly	missense_variant	2/3		NP_001397865.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCSAP	ENST00000284617.7 linkuse as main transcript	c.389A>G	p.Glu130Gly	missense_variant	3/4	1	NM_145257.5	ENSP00000284617	P1	Q6IQ19-1
CCSAP	ENST00000366687.5 linkuse as main transcript	c.389A>G	p.Glu130Gly	missense_variant	2/3	1		ENSP00000355648	P1	Q6IQ19-1
CCSAP	ENST00000483092.1 linkuse as main transcript	n.1372A>G		non_coding_transcript_exon_variant	3/4	1
CCSAP	ENST00000366686.1 linkuse as main transcript	c.47A>G	p.Glu16Gly	missense_variant	2/3	2		ENSP00000355647		Q6IQ19-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249296

Hom.:

AF XY:

0.0000297

AC XY:

AN XY:

134880

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000618

AC:

AN:

1456468

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

723612

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Dec 22, 2023

The c.389A>G (p.E130G) alteration is located in exon 3 (coding exon 2) of the CCSAP gene. This alteration results from a A to G substitution at nucleotide position 389, causing the glutamic acid (E) at amino acid position 130 to be replaced by a glycine (G). 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

0.092

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.058

T;T;.

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.094

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.69

T;.;T

M_CAP

Benign

0.055

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.32

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.092

Sift

Uncertain

0.025

D;D;D

Sift4G

Benign

0.13

T;T;D

Polyphen

0.63

P;P;.

Vest4

0.14

MutPred

0.19

Loss of solvent accessibility (P = 0.0387);Loss of solvent accessibility (P = 0.0387);.;

MVP

0.40

MPC

1.2

ClinPred

0.69

GERP RS

4.2

Varity_R

0.12

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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