12-49792516-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001037806.4(NCKAP5L):c.3722C>A(p.Ala1241Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,602 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 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: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
NCKAP5L
NM_001037806.4 missense
NM_001037806.4 missense
Scores
7
9
Clinical Significance
Conservation
PhyloP100: 3.95
Genes affected
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.08607417).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NCKAP5L | NM_001037806.4 | c.3722C>A | p.Ala1241Glu | missense_variant | 12/13 | ENST00000335999.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NCKAP5L | ENST00000335999.7 | c.3722C>A | p.Ala1241Glu | missense_variant | 12/13 | 5 | NM_001037806.4 | P1 | |
NCKAP5L | ENST00000433948.5 | c.2867C>A | p.Ala956Glu | missense_variant | 5/5 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000524 AC: 13AN: 248174Hom.: 0 AF XY: 0.0000446 AC XY: 6AN XY: 134652
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461434Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14AN XY: 727000
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
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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 01, 2022 | The c.3722C>A (p.A1241E) alteration is located in exon 12 (coding exon 10) of the NCKAP5L gene. This alteration results from a C to A substitution at nucleotide position 3722, causing the alanine (A) at amino acid position 1241 to be replaced by a glutamic acid (E). 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
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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