chr2-132731991-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_207363.3(NCKAP5):c.5189C>T(p.Ser1730Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000923 in 1,613,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 0 hom. )
Consequence
NCKAP5
NM_207363.3 missense
NM_207363.3 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 7.88
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2893374).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCKAP5 | NM_207363.3 | c.5189C>T | p.Ser1730Leu | missense_variant | 17/20 | ENST00000409261.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCKAP5 | ENST00000409261.6 | c.5189C>T | p.Ser1730Leu | missense_variant | 17/20 | 5 | NM_207363.3 | P1 | |
ENST00000651100.1 | n.457+45526G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000604 AC: 15AN: 248474Hom.: 0 AF XY: 0.0000519 AC XY: 7AN XY: 134798
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GnomAD4 exome AF: 0.0000965 AC: 141AN: 1461612Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 73AN XY: 727096
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GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74324
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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 | Dec 21, 2022 | The c.5189C>T (p.S1730L) alteration is located in exon 17 (coding exon 15) of the NCKAP5 gene. This alteration results from a C to T substitution at nucleotide position 5189, causing the serine (S) at amino acid position 1730 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.;.
MutationTaster
Benign
D;D;N;N
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Pathogenic
D;D;T;T
Polyphen
D;.;.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at