Variant 2-132728905-T-C 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_207363.3(NCKAP5):c.5491A>G(p.Thr1831Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000301 in 1,461,686 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: not found (cov: 32)

Exomes 𝑓: 0.000030 ( 1 hom. )

Consequence

NCKAP5
NM_207363.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.636

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:

ENSG00000286068 (HGNC:):

ENSG00000286068 links:

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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=0.044869035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCKAP5	NM_207363.3 linkuse as main transcript	c.5491A>G	p.Thr1831Ala	missense_variant	18/20	ENST00000409261.6	NP_997246.2	O14513-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCKAP5	ENST00000409261.6 linkuse as main transcript	c.5491A>G	p.Thr1831Ala	missense_variant	18/20	5	NM_207363.3	ENSP00000387128.1		O14513-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000602

AC:

AN:

249042

Hom.:

AF XY:

0.0000814

AC XY:

AN XY:

135086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1461686

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

Cov.:

Alfa

AF:

0.000211

Hom.:

ExAC

AF:

0.0000910

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 03, 2023

The c.5491A>G (p.T1831A) alteration is located in exon 18 (coding exon 16) of the NCKAP5 gene. This alteration results from a A to G substitution at nucleotide position 5491, causing the threonine (T) at amino acid position 1831 to be replaced by an alanine (A). 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

0.072

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0056

T;.;T;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.045

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.0

N;N;N;N

REVEL

Benign

0.019

Sift

Uncertain

0.011

D;D;D;D

Sift4G

Uncertain

0.016

D;D;T;T

Polyphen

0.021

B;.;.;B

Vest4

0.24

MutPred

0.10

Loss of phosphorylation at T1831 (P = 0.0137);Loss of phosphorylation at T1831 (P = 0.0137);.;.;

MVP

0.17

MPC

0.041

ClinPred

0.11

GERP RS

0.92

Varity_R

0.060

gMVP

0.25

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