15-73633441-A-G

Variant names:

• chr15-73633441-A-G
• rs3743500
• ENST00000351217.10:c.-226T>C

Variant summary

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

The ENST00000351217.10(NPTN):​c.-226T>C variant causes a 5 prime UTR 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NPTN ENST00000351217.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.501
• Publications: 7 publications found

Genes affected

NPTN (HGNC:17867): (neuroplastin) This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2009]

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 (BayesDel_noAF=-0.58).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000351217.10. 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
	NPTN	NM_012428.4	MANE Select	c.-226T>C		upstream_gene	N/A	NP_036560.1	Q9Y639-2
	NPTN	NM_001161363.2		c.-226T>C		upstream_gene	N/A	NP_001154835.1	Q9Y639-5
	NPTN	NM_017455.4		c.-226T>C		upstream_gene	N/A	NP_059429.1	Q9Y639-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPTN	ENST00000351217.10	TSL:1	c.-226T>C		5_prime_UTR	Exon 1 of 8	ENSP00000342958.6	Q9Y639-1
	NPTN	ENST00000970031.1		c.-226T>C		5_prime_UTR	Exon 1 of 6	ENSP00000640090.1
	NPTN	ENST00000345330.9	TSL:1 MANE Select	c.-226T>C		upstream_gene	N/A	ENSP00000290401.4	Q9Y639-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 3

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		-0.50
PromoterAI		-0.37	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3743500; hg19: chr15-73925782;