Variant 15-88032954-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001012338.3(NTRK3):c.1488C>G(p.Ala496Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 1,611,594 control chromosomes in the GnomAD database, including 100,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10141 hom., cov: 27)

Exomes 𝑓: 0.35 ( 90415 hom. )

Consequence

NTRK3
NM_001012338.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.466

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:

NTRK3 (HGNC:):

NTRK3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 15-88032954-G-C is Benign according to our data. Variant chr15-88032954-G-C is described in ClinVar as [Benign]. Clinvar id is 1251369.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.466 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3 linkuse as main transcript	c.1488C>G	p.Ala496Ala	synonymous_variant	14/20	ENST00000629765.3	NP_001012338.1	Q16288-1X5D2R1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3 linkuse as main transcript	c.1488C>G	p.Ala496Ala	synonymous_variant	14/20	1	NM_001012338.3	ENSP00000485864.1		Q16288-1

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

54911

AN:

150672

Hom.:

10129

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.253

Gnomad AMR

AF:

0.358

Gnomad ASJ

AF:

0.402

Gnomad EAS

AF:

0.220

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.288

Gnomad MID

AF:

0.448

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.357

GnomAD3 exomes

AF:

0.347

AC:

86645

AN:

249410

Hom.:

15453

AF XY:

0.350

AC XY:

47134

AN XY:

134772

show subpopulations

Gnomad AFR exome

AF:

0.415

Gnomad AMR exome

AF:

0.340

Gnomad ASJ exome

AF:

0.408

Gnomad EAS exome

AF:

0.206

Gnomad SAS exome

AF:

0.388

Gnomad FIN exome

AF:

0.294

Gnomad NFE exome

AF:

0.356

Gnomad OTH exome

AF:

0.353

GnomAD4 exome

AF:

0.349

AC:

510182

AN:

1460804

Hom.:

90415

Cov.:

AF XY:

0.351

AC XY:

254768

AN XY:

726582

show subpopulations

Gnomad4 AFR exome

AF:

0.419

Gnomad4 AMR exome

AF:

0.343

Gnomad4 ASJ exome

AF:

0.404

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.296

Gnomad4 NFE exome

AF:

0.350

Gnomad4 OTH exome

AF:

0.356

GnomAD4 genome

AF:

0.364

AC:

54944

AN:

150790

Hom.:

10141

Cov.:

AF XY:

0.362

AC XY:

26626

AN XY:

73570

show subpopulations

Gnomad4 AFR

AF:

0.414

Gnomad4 AMR

AF:

0.358

Gnomad4 ASJ

AF:

0.402

Gnomad4 EAS

AF:

0.220

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.288

Gnomad4 NFE

AF:

0.357

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.292

Hom.:

1175

Bravo

AF:

0.371

EpiCase

AF:

0.362

EpiControl

AF:

0.369

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Nov 12, 2018	- -

NTRK3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.060

DANN

Benign

0.66

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