NM_006157.5:c.249C>A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. 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. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NELL1 NM_006157.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0250
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006157.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	NM_006157.5	MANE Select	c.249C>A	p.Asn83Lys	missense	Exon 3 of 20	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.333C>A	p.Asn111Lys	missense	Exon 4 of 21	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.249C>A	p.Asn83Lys	missense	Exon 3 of 19	NP_963845.1	Q92832-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NELL1	ENST00000357134.10	TSL:1 MANE Select	c.249C>A	p.Asn83Lys	missense	Exon 3 of 20	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.249C>A	p.Asn83Lys	missense	Exon 3 of 19	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000298925.9	TSL:2	c.333C>A	p.Asn111Lys	missense	Exon 4 of 21	ENSP00000298925.5	J3KNC5

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 v4.9

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
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.39
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		0.025
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.079
Sift	Uncertain	0.026	D
Sift4G	Uncertain	0.052	T
Polyphen		0.66	P
Vest4		0.61
MutPred		0.47		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
Mutation Taster		=44/56	disease causing

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

Other links and lift over

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