Variant rs1128994 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001012338.3(NTRK3):c.573C>T(p.Asn191=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,613,770 control chromosomes in the GnomAD database, including 59,586 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.29 ( 6598 hom., cov: 33)

Exomes 𝑓: 0.27 ( 52988 hom. )

Consequence

NTRK3
NM_001012338.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.570

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 15-88137453-G-A is Benign according to our data. Variant chr15-88137453-G-A is described in ClinVar as [Benign]. Clinvar id is 1227513.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 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.573C>T	p.Asn191=	synonymous_variant	7/20	ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3 linkuse as main transcript	c.573C>T	p.Asn191=	synonymous_variant	7/20	1	NM_001012338.3		Q16288-1

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43764

AN:

152022

Hom.:

6584

Cov.:

show subpopulations

Gnomad AFR

AF:

0.372

Gnomad AMI

AF:

0.276

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.210

Gnomad NFE

AF:

0.269

Gnomad OTH

AF:

0.281

GnomAD3 exomes

AF:

0.257

AC:

64465

AN:

251146

Hom.:

8818

AF XY:

0.257

AC XY:

34909

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.377

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.343

Gnomad EAS exome

AF:

0.228

Gnomad SAS exome

AF:

0.269

Gnomad FIN exome

AF:

0.243

Gnomad NFE exome

AF:

0.268

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.267

AC:

389969

AN:

1461630

Hom.:

52988

Cov.:

AF XY:

0.267

AC XY:

194245

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.383

Gnomad4 AMR exome

AF:

0.155

Gnomad4 ASJ exome

AF:

0.343

Gnomad4 EAS exome

AF:

0.202

Gnomad4 SAS exome

AF:

0.268

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.268

Gnomad4 OTH exome

AF:

0.278

GnomAD4 genome

AF:

0.288

AC:

43819

AN:

152140

Hom.:

6598

Cov.:

AF XY:

0.285

AC XY:

21191

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.372

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.333

Gnomad4 EAS

AF:

0.228

Gnomad4 SAS

AF:

0.266

Gnomad4 FIN

AF:

0.239

Gnomad4 NFE

AF:

0.269

Gnomad4 OTH

AF:

0.284

Alfa

AF:

0.286

Hom.:

3187

Bravo

AF:

0.289

Asia WGS

AF:

0.259

AC:

902

AN:

3478

EpiCase

AF:

0.271

EpiControl

AF:

0.262

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.9

DANN

Benign

0.63

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