chr11-20677955-G-C

Variant names:

• chr11-20677955-G-C
• NM_006157.5:c.79G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006157.5(NELL1):​c.79G>C​(p.Asp27His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 5.54

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 2 ACMG points.

• 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.79G>C	p.Asp27His	missense_variant	Exon 2 of 20	ENST00000357134.10	NP_006148.2
NELL1	NM_001288713.1	c.163G>C	p.Asp55His	missense_variant	Exon 3 of 21		NP_001275642.1
NELL1	NM_201551.2	c.79G>C	p.Asp27His	missense_variant	Exon 2 of 19		NP_963845.1
NELL1	NM_001288714.1	c.79G>C	p.Asp27His	missense_variant	Exon 2 of 19		NP_001275643.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NELL1	ENST00000357134.10	c.79G>C	p.Asp27His	missense_variant	Exon 2 of 20	1	NM_006157.5	ENSP00000349654.5
NELL1	ENST00000532434.5	c.79G>C	p.Asp27His	missense_variant	Exon 2 of 19	1		ENSP00000437170.1
NELL1	ENST00000298925.9	c.163G>C	p.Asp55His	missense_variant	Exon 3 of 21	2		ENSP00000298925.5
NELL1	ENST00000325319.9	c.79G>C	p.Asp27His	missense_variant	Exon 2 of 19	2		ENSP00000317837.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 27, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.79G>C (p.D27H) alteration is located in exon 2 (coding exon 2) of the NELL1 gene. This alteration results from a G to C substitution at nucleotide position 79, causing the aspartic acid (D) at amino acid position 27 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.045	.;T;T;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.63
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.78	T;T;T;T
M_CAP	Benign	0.042	D
MetaRNN	Uncertain	0.54	D;D;D;D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Uncertain	2.5	.;.;M;M
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-1.8	N;N;N;N
REVEL	Uncertain	0.64
Sift	Uncertain	0.021	D;D;D;D
Sift4G	Benign	0.066	T;T;T;T
Polyphen		1.0	D;.;D;P
Vest4		0.51
MutPred		0.48		Loss of solvent accessibility (P = 0.0169);.;Loss of solvent accessibility (P = 0.0169);Loss of solvent accessibility (P = 0.0169);
MVP		0.92
MPC		0.10
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.27
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-20699501;