NM_006157.5:c.244C>G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006157.5(NELL1):​c.244C>G​(p.Arg82Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,624 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R82W) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

NELL1
NM_006157.5 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.62
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NELL1NM_006157.5 linkc.244C>G p.Arg82Gly missense_variant Exon 3 of 20 ENST00000357134.10 NP_006148.2 Q92832-1K9UUD5
NELL1NM_001288713.1 linkc.328C>G p.Arg110Gly missense_variant Exon 4 of 21 NP_001275642.1 Q92832J3KNC5K9UUD5B3KXR2
NELL1NM_201551.2 linkc.244C>G p.Arg82Gly missense_variant Exon 3 of 19 NP_963845.1 Q92832-2K9UUD5
NELL1NM_001288714.1 linkc.244C>G p.Arg82Gly missense_variant Exon 3 of 19 NP_001275643.1 Q92832F5H6I3K9UUD5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NELL1ENST00000357134.10 linkc.244C>G p.Arg82Gly missense_variant Exon 3 of 20 1 NM_006157.5 ENSP00000349654.5 Q92832-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461624
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
727114
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
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
Mar 04, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.244C>G (p.R82G) 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 244, causing the arginine (R) at amino acid position 82 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.056
T
BayesDel_noAF
Benign
-0.32
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.066
.;T;T;.
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Uncertain
0.94
D;D;D;D
M_CAP
Benign
0.013
T
MetaRNN
Pathogenic
0.77
D;D;D;D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.4
.;.;M;M
PrimateAI
Benign
0.37
T
PROVEAN
Pathogenic
-4.6
D;D;D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0080
D;D;D;D
Sift4G
Benign
0.082
T;D;D;D
Polyphen
0.49
P;.;B;P
Vest4
0.71
MutPred
0.56
Loss of stability (P = 0.021);.;Loss of stability (P = 0.021);Loss of stability (P = 0.021);
MVP
0.56
MPC
0.17
ClinPred
0.98
D
GERP RS
5.9
Varity_R
0.47
gMVP
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-20805285; API