chr11-20678049-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_006157.5(NELL1):c.173T>G(p.Phe58Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
NELL1
NM_006157.5 missense
NM_006157.5 missense
Scores
2
10
5
Clinical Significance
Conservation
PhyloP100: 5.16
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.815
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NELL1 | NM_006157.5 | c.173T>G | p.Phe58Cys | missense_variant | 2/20 | ENST00000357134.10 | |
NELL1 | NM_001288713.1 | c.257T>G | p.Phe86Cys | missense_variant | 3/21 | ||
NELL1 | NM_201551.2 | c.173T>G | p.Phe58Cys | missense_variant | 2/19 | ||
NELL1 | NM_001288714.1 | c.173T>G | p.Phe58Cys | missense_variant | 2/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELL1 | ENST00000357134.10 | c.173T>G | p.Phe58Cys | missense_variant | 2/20 | 1 | NM_006157.5 | P1 | |
NELL1 | ENST00000532434.5 | c.173T>G | p.Phe58Cys | missense_variant | 2/19 | 1 | |||
NELL1 | ENST00000298925.9 | c.257T>G | p.Phe86Cys | missense_variant | 3/21 | 2 | |||
NELL1 | ENST00000325319.9 | c.173T>G | p.Phe58Cys | 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 | Jan 02, 2024 | The c.173T>G (p.F58C) alteration is located in exon 2 (coding exon 2) of the NELL1 gene. This alteration results from a T to G substitution at nucleotide position 173, causing the phenylalanine (F) at amino acid position 58 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;.;P;D
Vest4
MutPred
Gain of catalytic residue at L59 (P = 0.0189);.;Gain of catalytic residue at L59 (P = 0.0189);Gain of catalytic residue at L59 (P = 0.0189);
MVP
MPC
0.49
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
Publications
No publications associated with this variant yet.