chr15-73052719-C-T

Variant names:

• chr15-73052719-C-T
• rs748943546
• NM_002499.4:c.44C>T

Variant summary

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

The NM_002499.4(NEO1):​c.44C>T​(p.Ser15Phe) 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. 13/21 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: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEO1 NM_002499.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

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=0.21267417).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEO1	NM_002499.4	c.44C>T	p.Ser15Phe	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.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 29	1	NM_002499.4	ENSP00000261908.6
NEO1	ENST00000558964.5	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 28	1		ENSP00000453200.1
NEO1	ENST00000560262.5	c.44C>T	p.Ser15Phe	missense_variant	Exon 1 of 28	1		ENSP00000453317.1
NEO1	ENST00000339362.9	c.44C>T	p.Ser15Phe	missense_variant	Exon 2 of 30	5		ENSP00000341198.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1207832 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 595256

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.091	T;T;.;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.80	.;T;T;T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.21	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;N;N;N
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.040	N;N;N;N
REVEL	Benign	0.081
Sift	Benign	0.077	T;T;T;T
Sift4G	Uncertain	0.025	D;D;D;D
Polyphen		0.68	P;P;.;.
Vest4		0.27
MutPred		0.48		Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);Loss of sheet (P = 3e-04);
MVP		0.58
MPC		0.20
ClinPred		0.12	T
GERP RS		0.013
Varity_R		0.069
gMVP		0.43

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: rs748943546; hg19: chr15-73345060;