chr15-73052712-A-G

Position:

• chr15-73052712-A-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.37A>G​(p.Thr13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000083 in 1,205,124 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: 8.3e-7 (0 hom.)
• Consequence: NEO1 NM_002499.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0440

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=0.094572425).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEO1	NM_002499.4	c.37A>G	p.Thr13Ala	missense_variant	1/29	ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.37A>G	p.Thr13Ala	missense_variant	1/29	1	NM_002499.4	ENSP00000261908.6
NEO1	ENST00000558964.5	c.37A>G	p.Thr13Ala	missense_variant	1/28	1		ENSP00000453200.1
NEO1	ENST00000560262.5	c.37A>G	p.Thr13Ala	missense_variant	1/28	1		ENSP00000453317.1
NEO1	ENST00000339362.9	c.37A>G	p.Thr13Ala	missense_variant	2/30	5		ENSP00000341198.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 8.30e-7 AC: 1 AN: 1205124 Hom.: 0 Cov.: 30 AF XY: 0.00000168 AC XY: 1 AN XY: 594320

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000102

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 29

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.37A>G (p.T13A) alteration is located in exon 1 (coding exon 1) of the NEO1 gene. This alteration results from a A to G substitution at nucleotide position 37, causing the threonine (T) at amino acid position 13 to be replaced by an alanine (A). 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	0.14
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.061	T;T;.;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.016	N
LIST_S2	Benign	0.54	.;T;T;T
M_CAP	Pathogenic	0.42	D
MetaRNN	Benign	0.095	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.20	N;N;N;N
REVEL	Benign	0.0030
Sift	Benign	0.23	T;T;T;T
Sift4G	Benign	0.32	T;T;T;T
Polyphen		0.0070	B;B;.;.
Vest4		0.042
MutPred		0.40		Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);Loss of sheet (P = 0.0025);
MVP		0.42
MPC		0.18
ClinPred		0.13	T
GERP RS		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.047
gMVP		0.45

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: chr15-73345053;