NM_006157.5:c.281A>G

Variant names:

• chr11-20783776-A-G
• NM_006157.5:c.281A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006157.5(NELL1):​c.281A>G​(p.Gln94Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NELL1 NM_006157.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.27
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21632367).

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.281A>G	p.Gln94Arg	missense	Exon 3 of 20	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.365A>G	p.Gln122Arg	missense	Exon 4 of 21	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.281A>G	p.Gln94Arg	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.281A>G	p.Gln94Arg	missense	Exon 3 of 20	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.281A>G	p.Gln94Arg	missense	Exon 3 of 19	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000298925.9	TSL:2	c.365A>G	p.Gln122Arg	missense	Exon 4 of 21	ENSP00000298925.5	J3KNC5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0013	T
Eigen	Benign	-0.15
Eigen_PC	Benign	0.059
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.97	L
PhyloP100		7.3
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.13
Sift	Benign	0.14	T
Sift4G	Benign	0.078	T
Polyphen		0.0050	B
Vest4		0.34
MutPred		0.45		Loss of ubiquitination at K96 (P = 0.0516)
MVP		0.49
MPC		0.092
ClinPred		0.81	D
GERP RS		4.8
Varity_R		0.13
gMVP		0.64
Mutation Taster		=67/33	polymorphism

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

hg19: chr11-20805322;