rs576614526

Variant names:

• chr11-20783744-C-A
• rs576614526
• NM_006157.5:c.249C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-20783744-C-A
• chr11-20783744-C-G
• chr11-20783744-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_006157.5(NELL1):​c.249C>A​(p.Asn83Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NELL1 NM_006157.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity NELL1_HUMAN
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NELL1	NM_006157.5	c.249C>A	p.Asn83Lys	missense_variant	Exon 3 of 20	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.333C>A	p.Asn111Lys	missense_variant	Exon 4 of 21		NP_001275642.1
NELL1	NM_201551.2	c.249C>A	p.Asn83Lys	missense_variant	Exon 3 of 19		NP_963845.1
NELL1	NM_001288714.1	c.249C>A	p.Asn83Lys	missense_variant	Exon 3 of 19		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.249C>A	p.Asn83Lys	missense_variant	Exon 3 of 20	1	NM_006157.5	ENSP00000349654.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.052	.;T;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.96	D;D;D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.73	D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	.;.;L;L
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Benign	0.079
Sift	Uncertain	0.026	D;D;D;D
Sift4G	Uncertain	0.052	T;T;T;T
Polyphen		0.66	P;.;P;B
Vest4		0.61
MutPred		0.47		Loss of stability (P = 0.0038);.;Loss of stability (P = 0.0038);Loss of stability (P = 0.0038);
MVP		0.43
MPC		0.11
ClinPred		0.81	D
GERP RS		-2.3
Varity_R		0.13
gMVP		0.32

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

LitVar

Other links and lift over

dbSNP: rs576614526; hg19: chr11-20805290; COSMIC: COSV54253279;