chr11-20847584-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006157.5(NELL1):c.337T>C(p.Tyr113His) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000685 in 1,459,660 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
NELL1
NM_006157.5 missense, splice_region
NM_006157.5 missense, splice_region
Scores
7
7
4
Splicing: ADA: 0.9311
2
Clinical Significance
Conservation
PhyloP100: 5.04
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.337T>C | p.Tyr113His | missense_variant, splice_region_variant | 4/20 | ENST00000357134.10 | |
NELL1 | NM_001288713.1 | c.421T>C | p.Tyr141His | missense_variant, splice_region_variant | 5/21 | ||
NELL1 | NM_201551.2 | c.337T>C | p.Tyr113His | missense_variant, splice_region_variant | 4/19 | ||
NELL1 | NM_001288714.1 | c.336-37860T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NELL1 | ENST00000357134.10 | c.337T>C | p.Tyr113His | missense_variant, splice_region_variant | 4/20 | 1 | NM_006157.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459660Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726056
GnomAD4 exome
AF:
AC:
1
AN:
1459660
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
726056
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
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 | Oct 27, 2023 | The c.337T>C (p.Y113H) alteration is located in exon 4 (coding exon 4) of the NELL1 gene. This alteration results from a T to C substitution at nucleotide position 337, causing the tyrosine (Y) at amino acid position 113 to be replaced by a histidine (H). 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
Pathogenic
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D
Sift4G
Pathogenic
D;D;D
Polyphen
1.0, 0.99
.;D;D
Vest4
MutPred
0.65
.;Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP
MPC
0.19
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
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.