Variant 11-46751513-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001008938.4(CKAP5):c.5155C>T(p.Leu1719=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000499 in 1,612,054 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00026 ( 3 hom. )

Consequence

CKAP5
NM_001008938.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.21

Variant links:

Genes affected

CKAP5 (HGNC:28959): (cytoskeleton associated protein 5) This gene encodes a cytoskeleton-associated protein which belongs to the TOG/XMAP215 family. The N-terminal half of this protein contains a microtubule-binding domain and the C-terminal half contains a KXGS motif for binding tubulin dimers. This protein has two distinct roles in spindle formation; it protects kinetochore microtubules from depolymerization and plays an essential role in centrosomal microtubule assembly. This protein may be necessary for the proper interaction of microtubules with the cell cortex for directional cell movement. It also plays a role in translation of the myelin basic protein (MBP) mRNA by interacting with heterogeneous nuclear ribonucleoprotein (hnRNP) A2, which associates with MBP. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Aug 2011]

CKAP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 11-46751513-G-A is Benign according to our data. Variant chr11-46751513-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2641752.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.21 with no splicing effect.

BS2

High AC in GnomAd4 at 420 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CKAP5	NM_001008938.4 linkuse as main transcript	c.5155C>T	p.Leu1719=	synonymous_variant	39/44	ENST00000529230.6	NP_001008938.1
CKAP5	NM_014756.4 linkuse as main transcript	c.4975C>T	p.Leu1659=	synonymous_variant	38/43		NP_055571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CKAP5	ENST00000529230.6 linkuse as main transcript	c.5155C>T	p.Leu1719=	synonymous_variant	39/44	5	NM_001008938.4	ENSP00000432768	P1	Q14008-1
CKAP5	ENST00000354558.7 linkuse as main transcript	c.4975C>T	p.Leu1659=	synonymous_variant	37/42	1		ENSP00000346566		Q14008-2
CKAP5	ENST00000533413.5 linkuse as main transcript	n.2134C>T		non_coding_transcript_exon_variant	14/19	1
CKAP5	ENST00000312055.9 linkuse as main transcript	c.4975C>T	p.Leu1659=	synonymous_variant	38/43	5		ENSP00000310227		Q14008-2

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

419

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00958

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000771

AC:

192

AN:

248930

Hom.:

AF XY:

0.000528

AC XY:

AN XY:

134538

show subpopulations

Gnomad AFR exome

AF:

0.00968

Gnomad AMR exome

AF:

0.000763

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000663

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000824

GnomAD4 exome

AF:

0.000263

AC:

384

AN:

1459774

Hom.:

Cov.:

AF XY:

0.000244

AC XY:

177

AN XY:

726104

show subpopulations

Gnomad4 AFR exome

AF:

0.00839

Gnomad4 AMR exome

AF:

0.000653

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000349

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000207

Gnomad4 OTH exome

AF:

0.000779

GnomAD4 genome

AF:

0.00276

AC:

420

AN:

152280

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00958

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.00301

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

CKAP5: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

5.6

DANN

Benign

0.62

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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