chr11-20885535-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006157.5(NELL1):āc.598T>Cā(p.Phe200Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000445 in 1,595,084 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 (ā ).
Frequency
Genomes: š 0.000053 ( 0 hom., cov: 32)
Exomes š: 0.000044 ( 0 hom. )
Consequence
NELL1
NM_006157.5 missense
NM_006157.5 missense
Scores
2
8
7
Clinical Significance
Conservation
PhyloP100: 4.65
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.37094268).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NELL1 | NM_006157.5 | c.598T>C | p.Phe200Leu | missense_variant | 5/20 | ENST00000357134.10 | |
LOC105376585 | XR_931106.3 | n.194-4678A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELL1 | ENST00000357134.10 | c.598T>C | p.Phe200Leu | missense_variant | 5/20 | 1 | NM_006157.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251240Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135778
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GnomAD4 exome AF: 0.0000437 AC: 63AN: 1442860Hom.: 0 Cov.: 26 AF XY: 0.0000473 AC XY: 34AN XY: 719108
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GnomAD4 genome AF: 0.0000526 AC: 8AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74382
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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 | Sep 26, 2022 | The c.598T>C (p.F200L) alteration is located in exon 5 (coding exon 5) of the NELL1 gene. This alteration results from a T to C substitution at nucleotide position 598, causing the phenylalanine (F) at amino acid position 200 to be replaced by a leucine (L). 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
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
B;.;B;B
Vest4
MutPred
0.62
.;.;Loss of methylation at K201 (P = 0.0462);Loss of methylation at K201 (P = 0.0462);
MVP
MPC
0.12
ClinPred
D
GERP RS
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gMVP
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