11-20677949-G-A

Variant names:

• chr11-20677949-G-A
• NM_006157.5:c.73G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006157.5(NELL1):​c.73G>A​(p.Asp25Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NELL1 NM_006157.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38953996).

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.73G>A	p.Asp25Asn	missense	Exon 2 of 20	NP_006148.2	Q92832-1
	NELL1	NM_001288713.1		c.157G>A	p.Asp53Asn	missense	Exon 3 of 21	NP_001275642.1	Q92832
	NELL1	NM_201551.2		c.73G>A	p.Asp25Asn	missense	Exon 2 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.73G>A	p.Asp25Asn	missense	Exon 2 of 20	ENSP00000349654.5	Q92832-1
	NELL1	ENST00000532434.5	TSL:1	c.73G>A	p.Asp25Asn	missense	Exon 2 of 19	ENSP00000437170.1	Q92832-2
	NELL1	ENST00000298925.9	TSL:2	c.157G>A	p.Asp53Asn	missense	Exon 3 of 21	ENSP00000298925.5	J3KNC5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

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	0.19
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.57	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.8
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.47
Sift	Uncertain	0.010	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.0060	B
Vest4		0.53
MutPred		0.34		Gain of helix (P = 0.2059)
MVP		0.87
MPC		0.12
ClinPred		0.88	D
GERP RS		5.2
Varity_R		0.20
gMVP		0.47
Mutation Taster		=79/21	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: chr11-20699495; COSMIC: COSV54255381;