11-20783744-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2
The NM_006157.5(NELL1):c.249C>G(p.Asn83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. 12/21 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: 0.0000068 ( 0 hom. )
Consequence
NELL1
NM_006157.5 missense
NM_006157.5 missense
Scores
7
10
Clinical Significance
Conservation
PhyloP100: 0.0250
Genes affected
NELL1 (HGNC:7750): (neural EGFL like 1) This gene encodes a cytoplasmic protein that contains epidermal growth factor (EGF)-like repeats. The encoded heterotrimeric protein may be involved in cell growth regulation and differentiation. A similar protein in rodents is involved in craniosynostosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM1
?
In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity NELL1_HUMAN
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NELL1 | NM_006157.5 | c.249C>G | p.Asn83Lys | missense_variant | 3/20 | ENST00000357134.10 | |
NELL1 | NM_001288713.1 | c.333C>G | p.Asn111Lys | missense_variant | 4/21 | ||
NELL1 | NM_201551.2 | c.249C>G | p.Asn83Lys | missense_variant | 3/19 | ||
NELL1 | NM_001288714.1 | c.249C>G | p.Asn83Lys | missense_variant | 3/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELL1 | ENST00000357134.10 | c.249C>G | p.Asn83Lys | missense_variant | 3/20 | 1 | NM_006157.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251308Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135806
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461674Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7AN XY: 727136
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152288Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74458
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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 | Jan 22, 2024 | The c.249C>G (p.N83K) alteration is located in exon 3 (coding exon 3) of the NELL1 gene. This alteration results from a C to G substitution at nucleotide position 249, causing the asparagine (N) at amino acid position 83 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
T;T;T;T
Polyphen
P;.;P;B
Vest4
MutPred
Loss of stability (P = 0.0038);.;Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);
MVP
MPC
0.11
ClinPred
T
GERP RS
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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