chr11-20678032-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006157.5(NELL1):c.156C>G(p.His52Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H52Y) has been classified as Uncertain significance.
Frequency
Genomes: not found (cov: 32)
Consequence
NELL1
NM_006157.5 missense
NM_006157.5 missense
Scores
6
11
Clinical Significance
Conservation
PhyloP100: 2.42
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 2 ACMG points.
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.156C>G | p.His52Gln | missense_variant | 2/20 | ENST00000357134.10 | |
NELL1 | NM_001288713.1 | c.240C>G | p.His80Gln | missense_variant | 3/21 | ||
NELL1 | NM_201551.2 | c.156C>G | p.His52Gln | missense_variant | 2/19 | ||
NELL1 | NM_001288714.1 | c.156C>G | p.His52Gln | missense_variant | 2/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELL1 | ENST00000357134.10 | c.156C>G | p.His52Gln | missense_variant | 2/20 | 1 | NM_006157.5 | P1 | |
NELL1 | ENST00000532434.5 | c.156C>G | p.His52Gln | missense_variant | 2/19 | 1 | |||
NELL1 | ENST00000298925.9 | c.240C>G | p.His80Gln | missense_variant | 3/21 | 2 | |||
NELL1 | ENST00000325319.9 | c.156C>G | p.His52Gln | missense_variant | 2/19 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Sep 20, 2023 | The c.156C>G (p.H52Q) alteration is located in exon 2 (coding exon 2) of the NELL1 gene. This alteration results from a C to G substitution at nucleotide position 156, causing the histidine (H) at amino acid position 52 to be replaced by a glutamine (Q). 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;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Uncertain
T;D;D;D
Polyphen
P;.;B;D
Vest4
MutPred
Gain of relative solvent accessibility (P = 0.0522);.;Gain of relative solvent accessibility (P = 0.0522);Gain of relative solvent accessibility (P = 0.0522);
MVP
MPC
0.46
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