Variant 2-132773891-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_207363.3(NCKAP5):c.5053A>C(p.Lys1685Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0013 in 1,609,296 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 2 hom. )

Consequence

NCKAP5
NM_207363.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

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 Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.036576778).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCKAP5	NM_207363.3 linkuse as main transcript	c.5053A>C	p.Lys1685Gln	missense_variant	16/20	ENST00000409261.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCKAP5	ENST00000409261.6 linkuse as main transcript	c.5053A>C	p.Lys1685Gln	missense_variant	16/20	5	NM_207363.3	P1	O14513-1
	ENST00000651100.1 linkuse as main transcript	n.458-40710T>G		intron_variant, non_coding_transcript_variant
NCKAP5	ENST00000409213.5 linkuse as main transcript	c.1096A>C	p.Lys366Gln	missense_variant	14/18	5			O14513-2
NCKAP5	ENST00000473859.1 linkuse as main transcript	n.262+7161A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

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:

0.00123

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000683

AC:

167

AN:

244496

Hom.:

AF XY:

0.000740

AC XY:

AN XY:

132458

show subpopulations

Gnomad AFR exome

AF:

0.000195

Gnomad AMR exome

AF:

0.000754

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00118

Gnomad OTH exome

AF:

0.00118

GnomAD4 exome

AF:

0.00136

AC:

1979

AN:

1456944

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

955

AN XY:

724544

show subpopulations

Gnomad4 AFR exome

AF:

0.000301

Gnomad4 AMR exome

AF:

0.000732

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00167

Gnomad4 OTH exome

AF:

0.00130

GnomAD4 genome

AF:

0.000794

AC:

121

AN:

152352

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00123

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000855

Hom.:

Bravo

AF:

0.000820

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.000272

AC:

ESP6500EA

AF:

0.000734

AC:

ExAC

AF:

0.000687

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000713

EpiControl

AF:

0.00113

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

May 25, 2022

The c.5053A>C (p.K1685Q) alteration is located in exon 16 (coding exon 14) of the NCKAP5 gene. This alteration results from a A to C substitution at nucleotide position 5053, causing the lysine (K) at amino acid position 1685 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.41

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.0088

T;.;T;.

Eigen

Benign

-0.044

Eigen_PC

Benign

-0.075

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.76

T;T;T;T

M_CAP

Benign

0.019

MetaRNN

Benign

0.037

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.7

M;.;.;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.071

T;T;T;T

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.98

D;.;.;P

Vest4

0.33

MVP

0.29

MPC

0.10

ClinPred

0.039

GERP RS

4.5

Varity_R

0.083

gMVP

0.12

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