Variant 15-87880232-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001012338.3(NTRK3):c.2334+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,612,112 control chromosomes in the GnomAD database, including 280,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20165 hom., cov: 31)

Exomes 𝑓: 0.59 ( 260552 hom. )

Consequence

NTRK3
NM_001012338.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.297

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 15-87880232-C-T is Benign according to our data. Variant chr15-87880232-C-T is described in ClinVar as [Benign]. Clinvar id is 1249082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3 linkuse as main transcript	c.2334+38G>A		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3 linkuse as main transcript	c.2334+38G>A		intron_variant		1	NM_001012338.3		Q16288-1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73877

AN:

151646

Hom.:

20158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.511

GnomAD3 exomes

AF:

0.547

AC:

137465

AN:

251166

Hom.:

39261

AF XY:

0.548

AC XY:

74454

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.598

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.574

GnomAD4 exome

AF:

0.591

AC:

863300

AN:

1460348

Hom.:

260552

Cov.:

AF XY:

0.587

AC XY:

426416

AN XY:

726540

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.546

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.622

Gnomad4 SAS exome

AF:

0.416

Gnomad4 FIN exome

AF:

0.581

Gnomad4 NFE exome

AF:

0.619

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.487

AC:

73890

AN:

151764

Hom.:

20165

Cov.:

AF XY:

0.486

AC XY:

36016

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.219

Gnomad4 AMR

AF:

0.547

Gnomad4 ASJ

AF:

0.609

Gnomad4 EAS

AF:

0.602

Gnomad4 SAS

AF:

0.420

Gnomad4 FIN

AF:

0.589

Gnomad4 NFE

AF:

0.610

Gnomad4 OTH

AF:

0.507

Alfa

AF:

0.589

Hom.:

45783

Bravo

AF:

0.477

Asia WGS

AF:

0.483

AC:

1684

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over