3-101801364-CGC-TGT

Variant names:

• chr3-101801364-CGC-TGT
• NM_145037.4:c.223_225delCGCinsTGT
• NXPE3 p.Arg75Cys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_145037.4(NXPE3):​c.223_225delCGCinsTGT​(p.Arg75Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R75H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NXPE3 NM_145037.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.27
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.223_225delCGCinsTGT	p.Arg75Cys	missense	N/A	NP_659474.1	Q969Y0
	NXPE3	NM_001134456.2		c.223_225delCGCinsTGT	p.Arg75Cys	missense	N/A	NP_001127928.1	Q969Y0
	NXPE3	NM_001348990.2		c.223_225delCGCinsTGT	p.Arg75Cys	missense	N/A	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.223_225delCGCinsTGT	p.Arg75Cys	missense	N/A	ENSP00000273347.5	Q969Y0
	NXPE3	ENST00000477909.5	TSL:1	c.223_225delCGCinsTGT	p.Arg75Cys	missense	N/A	ENSP00000418369.1	Q969Y0
	NXPE3	ENST00000474165.6	TSL:5	c.223_225delCGCinsTGT	p.Arg75Cys	missense	N/A	ENSP00000419667.2	C9K0A9

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr3-101520208;