chr15-73116812-A-C

Position:

• chr15-73116812-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002499.4(NEO1):​c.403A>C​(p.Ser135Arg) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NEO1 NM_002499.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.93

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27267992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NEO1	NM_002499.4	c.403A>C	p.Ser135Arg	missense_variant	2/29	ENST00000261908.11	NP_002490.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NEO1	ENST00000261908.11	c.403A>C	p.Ser135Arg	missense_variant	2/29	1	NM_002499.4	ENSP00000261908.6
NEO1	ENST00000558964.5	c.403A>C	p.Ser135Arg	missense_variant	2/28	1		ENSP00000453200.1
NEO1	ENST00000560262.5	c.403A>C	p.Ser135Arg	missense_variant	2/28	1		ENSP00000453317.1
NEO1	ENST00000339362.9	c.403A>C	p.Ser135Arg	missense_variant	3/30	5		ENSP00000341198.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Nov 23, 2024

The c.403A>C (p.S135R) alteration is located in exon 2 (coding exon 2) of the NEO1 gene. This alteration results from a A to C substitution at nucleotide position 403, causing the serine (S) at amino acid position 135 to be replaced by an arginine (R). 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	Pathogenic	0.68
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	.;D;D;D
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.17	N;N;N;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-2.2	N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.072	T;T;D;T
Sift4G	Uncertain	0.050	T;T;D;T
Polyphen		0.086	B;B;.;.
Vest4		0.52
MutPred		0.53		Gain of MoRF binding (P = 0.0157);Gain of MoRF binding (P = 0.0157);Gain of MoRF binding (P = 0.0157);Gain of MoRF binding (P = 0.0157);
MVP		0.25
MPC		0.42
ClinPred		0.93	D
GERP RS		4.8
Varity_R		0.19
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: chr15-73409153;