chr15-73633565-C-T

Position:

• chr15-73633565-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000351217.10(NPTN):​c.-350G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0561 in 225,142 control chromosomes in the GnomAD database, including 370 homozygotes. 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: 𝑓 0.057 (259 hom., cov: 32)
  • Exomes 𝑓: 0.055 (111 hom.)
• Consequence: NPTN ENST00000351217.10 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.297

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.084 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPTN	ENST00000351217.10	c.-350G>A		5_prime_UTR_variant	1/8	1

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8628 AN: 152170 Hom.: 257 Cov.: 32

Gnomad AFR AF: 0.0677

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0403

Gnomad ASJ AF: 0.0493

Gnomad EAS AF: 0.0690

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.0631

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0508

Gnomad OTH AF: 0.0517

GnomAD4 exome AF: 0.0546 AC: 3981 AN: 72854 Hom.: 111 Cov.: 0 AF XY: 0.0548 AC XY: 2059 AN XY: 37570

Gnomad4 AFR exome AF: 0.0846

Gnomad4 AMR exome AF: 0.0413

Gnomad4 ASJ exome AF: 0.0498

Gnomad4 EAS exome AF: 0.0604

Gnomad4 SAS exome AF: 0.0683

Gnomad4 FIN exome AF: 0.0683

Gnomad4 NFE exome AF: 0.0515

Gnomad4 OTH exome AF: 0.0543

GnomAD4 genome AF: 0.0568 AC: 8644 AN: 152288 Hom.: 259 Cov.: 32 AF XY: 0.0575 AC XY: 4283 AN XY: 74452

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.0402

Gnomad4 ASJ AF: 0.0493

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.0910

Gnomad4 FIN AF: 0.0631

Gnomad4 NFE AF: 0.0508

Gnomad4 OTH AF: 0.0531

Alfa AF: 0.0193 Hom.: 8

Bravo AF: 0.0541

Asia WGS AF: 0.0990 AC: 344 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	14
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3826047; hg19: chr15-73925906;