dbSNP rs201982587: CCSAP:p.Arg14Leu (chr1-229342425-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_145257.5(CCSAP):c.41G>T(p.Arg14Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000782 in 1,278,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R14H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.8e-7 ( 0 hom. )

Consequence

CCSAP
NM_145257.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.72

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29867044).

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.41G>T	p.Arg14Leu	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.41G>T	p.Arg14Leu	missense	Exon 2 of 4	ENSP00000284617.2	Q6IQ19-1
CCSAP	ENST00000366687.5	TSL:1	c.41G>T	p.Arg14Leu	missense	Exon 1 of 3	ENSP00000355648.1	Q6IQ19-1
CCSAP	ENST00000483092.1	TSL:1	n.472G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.82e-7

AC:

AN:

1278514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

629160

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

26522

American (AMR)

AF:

0.00

AC:

AN:

23636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19488

East Asian (EAS)

AF:

0.00

AC:

AN:

31134

South Asian (SAS)

AF:

0.00

AC:

AN:

60140

European-Finnish (FIN)

AF:

0.0000228

AC:

AN:

43822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4934

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1017536

Other (OTH)

AF:

0.00

AC:

AN:

51302

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.58

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.80

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.4

PhyloP100

1.7

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.063

Sift

Uncertain

0.029

Sift4G

Uncertain

0.011

Polyphen

0.87

Vest4

0.29

MVP

0.48

MPC

1.7

ClinPred

0.99

GERP RS

3.7

PromoterAI

0.039

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.40

gMVP

0.29

Mutation Taster

=66/34

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over