Variant 2-132781973-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_207363.3(NCKAP5):c.4838C>T(p.Thr1613Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000819 in 1,613,362 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 1 hom. )

Consequence

NCKAP5
NM_207363.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.98

Variant links:

Genes affected

NCKAP5 (HGNC:29847): (NCK associated protein 5) Predicted to be involved in microtubule bundle formation and microtubule depolymerization. Predicted to be active in microtubule plus-end. [provided by Alliance of Genome Resources, Apr 2022]

NCKAP5 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047915876).

BP6

Variant 2-132781973-G-A is Benign according to our data. Variant chr2-132781973-G-A is described in ClinVar as [Benign]. Clinvar id is 781820.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3 linkuse as main transcript	c.4838C>T	p.Thr1613Met	missense_variant	14/20	ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6 linkuse as main transcript	c.4838C>T	p.Thr1613Met	missense_variant	14/20	5	NM_207363.3	P1	O14513-1
	ENST00000651100.1 linkuse as main transcript	n.458-32628G>A		intron_variant, non_coding_transcript_variant
NCKAP5	ENST00000409213.5 linkuse as main transcript	c.1092+8050C>T		intron_variant		5			O14513-2
NCKAP5	ENST00000473859.1 linkuse as main transcript	n.51C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.00237

AC:

360

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000603

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000812

AC:

202

AN:

248714

Hom.:

AF XY:

0.000741

AC XY:

100

AN XY:

134890

show subpopulations

Gnomad AFR exome

AF:

0.00685

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000987

Gnomad FIN exome

AF:

0.0000465

Gnomad NFE exome

AF:

0.000673

Gnomad OTH exome

AF:

0.000828

GnomAD4 exome

AF:

0.000659

AC:

963

AN:

1461108

Hom.:

Cov.:

AF XY:

0.000647

AC XY:

470

AN XY:

726734

show subpopulations

Gnomad4 AFR exome

AF:

0.00992

Gnomad4 AMR exome

AF:

0.000246

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000478

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00236

AC:

359

AN:

152254

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00724

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000603

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000993

Hom.:

Bravo

AF:

0.00260

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00521

AC:

ESP6500EA

AF:

0.000605

AC:

ExAC

AF:

0.000844

AC:

102

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.0081

T;.

Eigen

Benign

0.032

Eigen_PC

Benign

0.040

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.084

Sift

Benign

0.045

D;D

Sift4G

Uncertain

0.0070

D;D

Polyphen

0.94

P;.

Vest4

0.13

MVP

0.043

MPC

0.26

ClinPred

0.019

GERP RS

5.1

Varity_R

0.035

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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