chr2-182928216-G-T
Position:
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_013436.5(NCKAP1):c.3081C>A(p.Asn1027Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
NCKAP1
NM_013436.5 missense
NM_013436.5 missense
Scores
8
6
5
Clinical Significance
Conservation
PhyloP100: 6.87
Genes affected
NCKAP1 (HGNC:7666): (NCK associated protein 1) Contributes to small GTPase binding activity. Involved in Rac protein signal transduction; positive regulation of Arp2/3 complex-mediated actin nucleation; and positive regulation of lamellipodium assembly. Located in extracellular exosome and focal adhesion. Part of SCAR complex. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, NCKAP1
PP3
MetaRNN computational evidence supports a deleterious effect, 0.976
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCKAP1 | NM_013436.5 | c.3081C>A | p.Asn1027Lys | missense_variant | 29/31 | ENST00000361354.9 | |
NCKAP1 | NM_205842.3 | c.3099C>A | p.Asn1033Lys | missense_variant | 30/32 | ||
NCKAP1 | XM_006712200.4 | c.3093C>A | p.Asn1031Lys | missense_variant | 30/32 | ||
NCKAP1 | XM_006712201.4 | c.3075C>A | p.Asn1025Lys | missense_variant | 29/31 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCKAP1 | ENST00000361354.9 | c.3081C>A | p.Asn1027Lys | missense_variant | 29/31 | 1 | NM_013436.5 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.86e-7 AC: 1AN: 1457648Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 725130
GnomAD4 exome
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1
AN:
1457648
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30
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0
AN XY:
725130
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2024 | The c.3099C>A (p.N1033K) alteration is located in exon 30 (coding exon 30) of the NCKAP1 gene. This alteration results from a C to A substitution at nucleotide position 3099, causing the asparagine (N) at amino acid position 1033 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;D
Vest4
MutPred
Gain of methylation at N1027 (P = 9e-04);.;
MVP
MPC
2.5
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at