15-73052778-A-G

Variant names:

• chr15-73052778-A-G
• rs773350771
• NM_002499.4:c.103A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002499.4(NEO1):​c.103A>G​(p.Arg35Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000294 in 1,020,636 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 29)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: NEO1 NM_002499.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

Genes affected

NEO1 (HGNC:7754): (neogenin 1) This gene encodes a cell surface protein that is a member of the immunoglobulin superfamily. The encoded protein consists of four N-terminal immunoglobulin-like domains, six fibronectin type III domains, a transmembrane domain and a C-terminal internal domain that shares homology with the tumor suppressor candidate gene DCC. This protein may be involved in cell growth and differentiation and in cell-cell adhesion. Defects in this gene are associated with cell proliferation in certain cancers. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12046626).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEO1	NM_002499.4	c.103A>G	p.Arg35Gly	missense_variant	Exon 1 of 29	ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.103A>G	p.Arg35Gly	missense_variant	Exon 1 of 29	1	NM_002499.4	ENSP00000261908.6
NEO1	ENST00000558964.5	c.103A>G	p.Arg35Gly	missense_variant	Exon 1 of 28	1		ENSP00000453200.1
NEO1	ENST00000560262.5	c.103A>G	p.Arg35Gly	missense_variant	Exon 1 of 28	1		ENSP00000453317.1
NEO1	ENST00000339362.9	c.103A>G	p.Arg35Gly	missense_variant	Exon 2 of 30	5		ENSP00000341198.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000294 AC: 3 AN: 1020636 Hom.: 0 Cov.: 20 AF XY: 0.00000202 AC XY: 1 AN XY: 496114

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000170

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	20
DANN	Benign	0.94
DEOGEN2	Benign	0.12	T;T;.;.
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.79	.;T;T;T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.36	N;N;N;N
REVEL	Benign	0.068
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Benign	0.15	T;T;T;T
Polyphen		0.0	B;B;.;.
Vest4		0.10
MutPred		0.45		Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);Loss of helix (P = 0.0017);
MVP		0.25
MPC		0.24
ClinPred		0.074	T
GERP RS		-0.014
Varity_R		0.16
gMVP		0.44

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: rs773350771; hg19: chr15-73345119;