chr11-20919317-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_006157.5(NELL1):c.742G>T(p.Ala248Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,601,334 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
NELL1
NM_006157.5 missense
NM_006157.5 missense
Scores
4
5
8
Clinical Significance
Conservation
PhyloP100: 9.32
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 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.08710754).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NELL1 | NM_006157.5 | c.742G>T | p.Ala248Ser | missense_variant | 7/20 | ENST00000357134.10 | |
LOC105376585 | XR_931106.3 | n.84+7396C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELL1 | ENST00000357134.10 | c.742G>T | p.Ala248Ser | missense_variant | 7/20 | 1 | NM_006157.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 151978Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000338 AC: 84AN: 248298Hom.: 0 AF XY: 0.000306 AC XY: 41AN XY: 134098
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GnomAD4 exome AF: 0.000202 AC: 293AN: 1449238Hom.: 0 Cov.: 26 AF XY: 0.000182 AC XY: 131AN XY: 721168
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GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152096Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74388
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3476
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 | Feb 23, 2023 | The c.742G>T (p.A248S) alteration is located in exon 7 (coding exon 7) of the NELL1 gene. This alteration results from a G to T substitution at nucleotide position 742, causing the alanine (A) at amino acid position 248 to be replaced by a serine (S). 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
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Uncertain
D;D;D;D
Polyphen
D;.;D;D
Vest4
MVP
MPC
0.19
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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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