rs16941261

Variant names:

• chr15-88112289-G-C
• rs16941261
• NM_001012338.3:c.1396+13982C>G

Variant summary

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

The NM_001012338.3(NTRK3):​c.1396+13982C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,116 control chromosomes in the GnomAD database, including 5,585 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 0.26 (5585 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.202
• Publications: 15 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1396+13982C>G		intron_variant	Intron 13 of 19	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1396+13982C>G		intron_variant	Intron 13 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39396 AN: 151998 Hom.: 5580 Cov.: 33

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0887

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.232

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

GnomAD4 genome AF: 0.259 AC: 39431 AN: 152116 Hom.: 5585 Cov.: 33 AF XY: 0.252 AC XY: 18735 AN XY: 74382

African (AFR) AF: 0.351 AC: 14562 AN: 41486

American (AMR) AF: 0.257 AC: 3933 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 733 AN: 3466

East Asian (EAS) AF: 0.0891 AC: 461 AN: 5174

South Asian (SAS) AF: 0.178 AC: 860 AN: 4824

European-Finnish (FIN) AF: 0.163 AC: 1721 AN: 10566

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.240 AC: 16317 AN: 67984

Other (OTH) AF: 0.233 AC: 494 AN: 2116

Alfa AF: 0.249 Hom.: 538

Bravo AF: 0.268

Asia WGS AF: 0.180 AC: 627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.1
DANN	Benign	0.66
PhyloP100		-0.20
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: rs16941261; hg19: chr15-88655520;