rs11633200

Positions:

• chr15-87885845-A-G
• chr15-87885845-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001012338.3(NTRK3):​c.2134-110T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 417,606 control chromosomes in the GnomAD database, including 72,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (22393 hom., cov: 31)
  • Exomes 𝑓: 0.60 (49742 hom.)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.642

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 15-87885845-A-G is Benign according to our data. Variant chr15-87885845-A-G is described in ClinVar as [Benign]. Clinvar id is 1223297.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.2134-110T>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.2134-110T>C		intron_variant		1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79531 AN: 151594 Hom.: 22387 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.606

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.605 AC: 160751 AN: 265894 Hom.: 49742 AF XY: 0.604 AC XY: 81682 AN XY: 135290

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.576

Gnomad4 ASJ exome AF: 0.623

Gnomad4 EAS exome AF: 0.646

Gnomad4 SAS exome AF: 0.411

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.624

Gnomad4 OTH exome AF: 0.583

GnomAD4 genome AF: 0.524 AC: 79548 AN: 151712 Hom.: 22393 Cov.: 31 AF XY: 0.524 AC XY: 38848 AN XY: 74148

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.607

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.606

Gnomad4 NFE AF: 0.632

Gnomad4 OTH AF: 0.539

Alfa AF: 0.413 Hom.: 1503

Bravo AF: 0.516

Asia WGS AF: 0.499 AC: 1733 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.84

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: rs11633200; hg19: chr15-88429076;