chr15-87978049-C-G

Position:

• chr15-87978049-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000629765.3(NTRK3):​c.1586-37296G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 232,960 control chromosomes in the GnomAD database, including 45,227 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 0.63 (31291 hom., cov: 33)
  • Exomes 𝑓: 0.57 (13936 hom.)
• Consequence: NTRK3 ENST00000629765.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.208

Genes affected

NTRK3 (HGNC:8033): (neurotrophic receptor tyrosine kinase 3) This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation and may play a role in the development of proprioceptive neurons that sense body position. Mutations in this gene have been associated with medulloblastomas, secretory breast carcinomas and other cancers. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1586-37296G>C		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1586-37296G>C		intron_variant		1	NM_001012338.3	ENSP00000485864

Frequencies

GnomAD3 genomes AF: 0.625 AC: 95011 AN: 151986 Hom.: 31222 Cov.: 33

Gnomad AFR AF: 0.832

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.605

Gnomad ASJ AF: 0.467

Gnomad EAS AF: 0.803

Gnomad SAS AF: 0.537

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.606

GnomAD4 exome AF: 0.575 AC: 46489 AN: 80856 Hom.: 13936 Cov.: 0 AF XY: 0.572 AC XY: 21392 AN XY: 37366

Gnomad4 AFR exome AF: 0.844

Gnomad4 AMR exome AF: 0.609

Gnomad4 ASJ exome AF: 0.471

Gnomad4 EAS exome AF: 0.787

Gnomad4 SAS exome AF: 0.524

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.517

Gnomad4 OTH exome AF: 0.569

GnomAD4 genome AF: 0.625 AC: 95138 AN: 152104 Hom.: 31291 Cov.: 33 AF XY: 0.623 AC XY: 46292 AN XY: 74328

Gnomad4 AFR AF: 0.832

Gnomad4 AMR AF: 0.606

Gnomad4 ASJ AF: 0.467

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.607

Alfa AF: 0.561 Hom.: 3098

Bravo AF: 0.646

Asia WGS AF: 0.676 AC: 2353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs28521337; hg19: chr15-88521280; COSMIC: COSV58124966; COSMIC: COSV58124966;