15-73052728-T-C

Variant names:

• chr15-73052728-T-C
• NM_002499.4:c.53T>C

Variant summary

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

The NM_002499.4(NEO1):​c.53T>C​(p.Leu18Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 (★). Synonymous variant affecting the same amino acid position (i.e. L18L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEO1 NM_002499.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.327

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=0.23246384).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEO1	NM_002499.4	c.53T>C	p.Leu18Pro	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.53T>C	p.Leu18Pro	missense_variant	Exon 1 of 29	1	NM_002499.4	ENSP00000261908.6
NEO1	ENST00000558964.5	c.53T>C	p.Leu18Pro	missense_variant	Exon 1 of 28	1		ENSP00000453200.1
NEO1	ENST00000560262.5	c.53T>C	p.Leu18Pro	missense_variant	Exon 1 of 28	1		ENSP00000453317.1
NEO1	ENST00000339362.9	c.53T>C	p.Leu18Pro	missense_variant	Exon 2 of 30	5		ENSP00000341198.5

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1190842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 586120

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: 0.00

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 provided Uncertain:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.22	T;T;.;.
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.68	.;T;T;T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.23	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-1.4	N;N;N;N
REVEL	Uncertain	0.30
Sift	Uncertain	0.0060	D;D;D;D
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.62	P;P;.;.
Vest4		0.31
MutPred		0.73		Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);Loss of sheet (P = 0.0037);
MVP		0.77
MPC		0.33
ClinPred		0.15	T
GERP RS		0.62
Varity_R		0.37
gMVP		0.60

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: chr15-73345069;