chr3-101801427-C-T

Variant names:

• chr3-101801427-C-T
• rs267599518
• NM_145037.4:c.286C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145037.4(NXPE3):​c.286C>T​(p.Pro96Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NXPE3 NM_145037.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.795
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058285385).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145037.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPE3	NM_145037.4	MANE Select	c.286C>T	p.Pro96Ser	missense	Exon 5 of 8	NP_659474.1	Q969Y0
	NXPE3	NM_001134456.2		c.286C>T	p.Pro96Ser	missense	Exon 5 of 8	NP_001127928.1	Q969Y0
	NXPE3	NM_001348990.2		c.286C>T	p.Pro96Ser	missense	Exon 5 of 8	NP_001335919.1	Q969Y0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NXPE3	ENST00000273347.10	TSL:1 MANE Select	c.286C>T	p.Pro96Ser	missense	Exon 5 of 8	ENSP00000273347.5	Q969Y0
	NXPE3	ENST00000477909.5	TSL:1	c.286C>T	p.Pro96Ser	missense	Exon 4 of 7	ENSP00000418369.1	Q969Y0
	NXPE3	ENST00000474165.6	TSL:5	c.286C>T	p.Pro96Ser	missense	Exon 6 of 9	ENSP00000419667.2	C9K0A9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461892 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727246

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.037	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.068
FATHMM_MKL	Benign	0.60	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.80
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.10	N
REVEL	Benign	0.047
Sift	Benign	0.48	T
Sift4G	Benign	0.17	T
Polyphen		0.026	B
Vest4		0.23
MutPred		0.43		Gain of sheet (P = 0.0221)
MVP		0.12
ClinPred		0.15	T
GERP RS		5.7
Varity_R		0.040
gMVP		0.46
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs267599518; hg19: chr3-101520271; COSMIC: COSV56289288; COSMIC: COSV56289288;