rs3840846

Variant names:

• chr15-73633677-CA-C
• rs3840846
• ENST00000351217.10:c.-463delT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000351217.10(NPTN):​c.-463delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0146 in 156,178 control chromosomes in the GnomAD database, including 28 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.015 (27 hom., cov: 32)
  • Exomes 𝑓: 0.014 (1 hom.)
• Consequence: NPTN ENST00000351217.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.822
• Publications: 2 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: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0146 (2229/152352) while in subpopulation EAS AF = 0.0542 (281/5184). AF 95% confidence interval is 0.049. There are 27 homozygotes in GnomAd4. There are 1107 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2229 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPTN	ENST00000351217.10	c.-463delT		5_prime_UTR_variant	Exon 1 of 8	1		ENSP00000342958.6

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2228 AN: 152234 Hom.: 27 Cov.: 32

Gnomad AFR AF: 0.0148

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.0541

Gnomad SAS AF: 0.00703

Gnomad FIN AF: 0.00357

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0148

Gnomad OTH AF: 0.0143

GnomAD4 exome AF: 0.0136 AC: 52 AN: 3826 Hom.: 1 Cov.: 0 AF XY: 0.0124 AC XY: 27 AN XY: 2174

African (AFR) AF: 0.0133 AC: 2 AN: 150

American (AMR) AF: 0.00 AC: 0 AN: 56

Ashkenazi Jewish (ASJ) AF: 0.00769 AC: 1 AN: 130

East Asian (EAS) AF: 0.0588 AC: 8 AN: 136

South Asian (SAS) AF: 0.00478 AC: 2 AN: 418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 138

Middle Eastern (MID) AF: 0.0385 AC: 1 AN: 26

European-Non Finnish (NFE) AF: 0.0135 AC: 34 AN: 2524

Other (OTH) AF: 0.0161 AC: 4 AN: 248

GnomAD4 genome AF: 0.0146 AC: 2229 AN: 152352 Hom.: 27 Cov.: 32 AF XY: 0.0149 AC XY: 1107 AN XY: 74506

African (AFR) AF: 0.0148 AC: 616 AN: 41580

American (AMR) AF: 0.0108 AC: 166 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0138 AC: 48 AN: 3472

East Asian (EAS) AF: 0.0542 AC: 281 AN: 5184

South Asian (SAS) AF: 0.00704 AC: 34 AN: 4832

European-Finnish (FIN) AF: 0.00357 AC: 38 AN: 10632

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0148 AC: 1009 AN: 68024

Other (OTH) AF: 0.0142 AC: 30 AN: 2114

Alfa AF: 0.00171 Hom.: 0

Bravo AF: 0.0152

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.82
Mutation Taster		=300/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs3840846; hg19: chr15-73926018;