chr3-101801592-CTCAAGCTG-C

Variant names:

• chr3-101801592-CTCAAGCTG-C
• rs863223380
• NM_145037.4:c.452_459delTCAAGCTG

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP6

The NM_145037.4(NXPE3):​c.452_459delTCAAGCTG​(p.Leu151ProfsTer29) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NXPE3 NM_145037.4 frameshift
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.99
• Publications: 1 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 3-101801592-CTCAAGCTG-C is Benign according to our data. Variant chr3-101801592-CTCAAGCTG-C is described in ClinVar as Benign. ClinVar VariationId is 208920.Status of the report is no_assertion_criteria_provided, 0 stars.

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.452_459delTCAAGCTG	p.Leu151ProfsTer29	frameshift	Exon 5 of 8	NP_659474.1	Q969Y0
	NXPE3	NM_001134456.2		c.452_459delTCAAGCTG	p.Leu151ProfsTer29	frameshift	Exon 5 of 8	NP_001127928.1	Q969Y0
	NXPE3	NM_001348990.2		c.452_459delTCAAGCTG	p.Leu151ProfsTer29	frameshift	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.452_459delTCAAGCTG	p.Leu151ProfsTer29	frameshift	Exon 5 of 8	ENSP00000273347.5	Q969Y0
	NXPE3	ENST00000477909.5	TSL:1	c.452_459delTCAAGCTG	p.Leu151ProfsTer29	frameshift	Exon 4 of 7	ENSP00000418369.1	Q969Y0
	NXPE3	ENST00000474165.6	TSL:5	c.452_459delTCAAGCTG	p.Leu151ProfsTer29	frameshift	Exon 6 of 9	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

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	Abnormality of neuronal migration (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.0
Mutation Taster		=19/181	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs863223380; hg19: chr3-101520436;