Genetic Variant CCSAP:p.Arg14His (chr1-229342425-C-T) – 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.41G>A(p.Arg14His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000391 in 1,278,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

CCSAP
NM_145257.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13697574).

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>A	p.Arg14His	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>A	p.Arg14His	missense	Exon 2 of 4	ENSP00000284617.2	Q6IQ19-1
CCSAP	ENST00000366687.5	TSL:1	c.41G>A	p.Arg14His	missense	Exon 1 of 3	ENSP00000355648.1	Q6IQ19-1
CCSAP	ENST00000483092.1	TSL:1	n.472G>A		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000391

AC:

AN:

1278518

Hom.:

Cov.:

AF XY:

0.00000477

AC XY:

AN XY:

629160

show subpopulations

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:

60142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43822

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4934

European-Non Finnish (NFE)

AF:

0.00000491

AC:

AN:

1017538

Other (OTH)

AF:

0.00

AC:

AN:

51302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.585

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:

0.00000378

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

Uncertain

0.46

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.062

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.0091

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.84

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.88

MutationAssessor

Benign

1.7

PhyloP100

1.7

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.092

Sift

Uncertain

0.026

Sift4G

Uncertain

0.010

Polyphen

0.10

Vest4

0.18

MutPred

0.18

Loss of MoRF binding (P = 0.0266)

MVP

0.36

MPC

1.7

ClinPred

0.91

GERP RS

3.7

PromoterAI

0.055

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

gMVP

0.18

Mutation Taster

=75/25

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over