2-132725742-C-T

Variant summary

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

The NM_207363.3(NCKAP5):​c.5598G>A​(p.Met1866Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,226 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NCKAP5
NM_207363.3 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.626
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]

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=0.04781258).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCKAP5NM_207363.3 linkc.5598G>A p.Met1866Ile missense_variant Exon 19 of 20 ENST00000409261.6 NP_997246.2 O14513-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NCKAP5ENST00000409261.6 linkc.5598G>A p.Met1866Ile missense_variant Exon 19 of 20 5 NM_207363.3 ENSP00000387128.1 O14513-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152200
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000147
Gnomad OTH
AF:
0.000478
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461026
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726772
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152200
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74350
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000478
Bravo
AF:
0.0000189

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 14, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5598G>A (p.M1866I) alteration is located in exon 19 (coding exon 17) of the NCKAP5 gene. This alteration results from a G to A substitution at nucleotide position 5598, causing the methionine (M) at amino acid position 1866 to be replaced by an isoleucine (I). 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
0.30
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
15
DANN
Benign
0.92
DEOGEN2
Benign
0.0054
T;.;T;.
Eigen
Benign
-0.72
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.15
N
LIST_S2
Benign
0.67
T;T;T;T
M_CAP
Benign
0.0063
T
MetaRNN
Benign
0.048
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.90
L;.;.;.
PrimateAI
Benign
0.45
T
PROVEAN
Benign
-0.14
N;N;N;N
REVEL
Benign
0.038
Sift
Benign
0.20
T;T;T;T
Sift4G
Benign
0.38
T;T;D;D
Polyphen
0.0020
B;.;.;B
Vest4
0.11
MutPred
0.25
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);.;.;
MVP
0.16
MPC
0.042
ClinPred
0.086
T
GERP RS
-1.4
Varity_R
0.069
gMVP
0.070

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs1690393369; hg19: chr2-133483315; API