Variant 1-229342129-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145257.5(CCSAP):c.337G>A(p.Ala113Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000259 in 1,342,160 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

CCSAP
NM_145257.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.656

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.003380984).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCSAP	NM_145257.5 linkuse as main transcript	c.337G>A	p.Ala113Thr	missense_variant	2/4	ENST00000284617.7	NP_660300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCSAP	ENST00000284617.7 linkuse as main transcript	c.337G>A	p.Ala113Thr	missense_variant	2/4	1	NM_145257.5	ENSP00000284617	P1	Q6IQ19-1
CCSAP	ENST00000366687.5 linkuse as main transcript	c.337G>A	p.Ala113Thr	missense_variant	1/3	1		ENSP00000355648	P1	Q6IQ19-1
CCSAP	ENST00000483092.1 linkuse as main transcript	n.768G>A		non_coding_transcript_exon_variant	2/4	1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000917

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.000806

AC:

AN:

45928

Hom.:

AF XY:

0.000830

AC XY:

AN XY:

26506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000929

Gnomad ASJ exome

AF:

0.00485

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000485

Gnomad OTH exome

AF:

0.00233

GnomAD4 exome

AF:

0.000250

AC:

298

AN:

1190162

Hom.:

Cov.:

AF XY:

0.000254

AC XY:

147

AN XY:

578910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000811

Gnomad4 AMR exome

AF:

0.00117

Gnomad4 ASJ exome

AF:

0.00300

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000229

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000664

GnomAD4 genome

AF:

0.000329

AC:

AN:

151998

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000916

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00143

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.000487

ExAC

AF:

0.000192

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

Sep 30, 2021

The c.337G>A (p.A113T) alteration is located in exon 2 (coding exon 1) of the CCSAP gene. This alteration results from a G to A substitution at nucleotide position 337, causing the alanine (A) at amino acid position 113 to be replaced by a threonine (T). 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

0.082

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0091

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.41

T;.

M_CAP

Benign

0.0098

MetaRNN

Benign

0.0034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.50

N;N

REVEL

Benign

0.035

Sift

Benign

0.56

T;T

Sift4G

Benign

0.37

T;T

Polyphen

0.0020

B;B

Vest4

0.11

MutPred

0.18

Gain of phosphorylation at A113 (P = 0.0083);Gain of phosphorylation at A113 (P = 0.0083);

MVP

0.040

MPC

0.41

ClinPred

0.018

GERP RS

-0.14

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.039

gMVP

0.049

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