3-101801877-C-T

Position:

• chr3-101801877-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_145037.4(NXPE3):​c.736C>T​(p.Pro246Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: NXPE3 NM_145037.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.05

Genes affected

NXPE3 (HGNC:28238): (neurexophilin and PC-esterase domain family member 3) This gene encodes a member of the neurexophilin family of neuropeptide-like glycoproteins. The encoded protein contains a variable N-terminal domain, a highly conserved neurexophilin and PC-esterase (NXPE) central domain, a short linker region, and a cysteine-rich C-terminal domain. This protein binds alpha neurexins, a group of presynaptic transmembrane receptors that promote adhesion between dendrites and axons. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

NXPE3 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.781

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NXPE3	NM_145037.4	c.736C>T	p.Pro246Ser	missense_variant	5/8	ENST00000273347.10	NP_659474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NXPE3	ENST00000273347.10	c.736C>T	p.Pro246Ser	missense_variant	5/8	1	NM_145037.4	ENSP00000273347.5

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

Sep 26, 2024

The c.736C>T (p.P246S) alteration is located in exon 5 (coding exon 2) of the NXPE3 gene. This alteration results from a C to T substitution at nucleotide position 736, causing the proline (P) at amino acid position 246 to be replaced by a serine (S). 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	Uncertain	0.40
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.032	T;T;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Pathogenic	0.98	.;.;D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.78	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M;M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-3.9	D;D;D
REVEL	Uncertain	0.39
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.32	T;T;T
Polyphen		1.0	D;D;D
Vest4		0.80
MutPred		0.52		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.22
ClinPred		0.98	D
GERP RS		5.8
Varity_R		0.26
gMVP		0.80

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: chr3-101520721; COSMIC: COSV56292485; COSMIC: COSV56292485;