15-87954910-A-T

Variant names:

• chr15-87954910-A-T
• rs7170215
• NM_001012338.3:c.1586-14157T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012338.3(NTRK3):​c.1586-14157T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,054 control chromosomes in the GnomAD database, including 20,166 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 0.51 (20166 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 6 publications found

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]

NTRK3 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1586-14157T>A		intron_variant	Intron 14 of 19	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1586-14157T>A		intron_variant	Intron 14 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76895 AN: 151934 Hom.: 20127 Cov.: 33

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.480

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.506 AC: 76988 AN: 152054 Hom.: 20166 Cov.: 33 AF XY: 0.504 AC XY: 37448 AN XY: 74328

African (AFR) AF: 0.639 AC: 26487 AN: 41470

American (AMR) AF: 0.449 AC: 6853 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.521 AC: 1808 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1404 AN: 5160

South Asian (SAS) AF: 0.543 AC: 2620 AN: 4822

European-Finnish (FIN) AF: 0.410 AC: 4334 AN: 10582

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32091 AN: 67968

Other (OTH) AF: 0.482 AC: 1016 AN: 2108

Alfa AF: 0.490 Hom.: 1967

Bravo AF: 0.510

Asia WGS AF: 0.431 AC: 1499 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.62
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7170215; hg19: chr15-88498141;