Genetic Variant CCSAP:p.Glu59Gln (chr1-229342291-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145257.5(CCSAP):c.175G>C(p.Glu59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000239 in 1,253,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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: 0.0000024 ( 0 hom. )

Consequence

CCSAP
NM_145257.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10303369).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145257.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCSAP	NM_145257.5	MANE Select	c.175G>C	p.Glu59Gln	missense	Exon 2 of 4	NP_660300.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CCSAP	ENST00000284617.7	TSL:1 MANE Select	c.175G>C	p.Glu59Gln	missense	Exon 2 of 4	ENSP00000284617.2	Q6IQ19-1
CCSAP	ENST00000366687.5	TSL:1	c.175G>C	p.Glu59Gln	missense	Exon 1 of 3	ENSP00000355648.1	Q6IQ19-1
CCSAP	ENST00000483092.1	TSL:1	n.606G>C		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000239

AC:

AN:

1253426

Hom.:

Cov.:

AF XY:

0.00000324

AC XY:

AN XY:

616342

show subpopulations

African (AFR)

AF:

0.0000756

AC:

AN:

26446

American (AMR)

AF:

0.00

AC:

AN:

21842

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20558

East Asian (EAS)

AF:

0.00

AC:

AN:

28982

South Asian (SAS)

AF:

0.00

AC:

AN:

59190

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3678

European-Non Finnish (NFE)

AF:

9.89e-7

AC:

AN:

1011010

Other (OTH)

AF:

0.00

AC:

AN:

50732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.018

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.49

M_CAP

Benign

0.014

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

1.6

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.2

REVEL

Benign

0.049

Sift

Benign

0.12

Sift4G

Benign

0.34

Polyphen

0.26

Vest4

0.061

MutPred

0.10

Loss of phosphorylation at S57 (P = 0.168)

MVP

0.24

MPC

1.4

ClinPred

0.43

GERP RS

4.2

PromoterAI

0.0094

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.12

gMVP

0.22

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over