Genetic Variant NTRK3:c.2134-110T>A (chr15-87885845-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001012338.3(NTRK3):c.2134-110T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,656 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NTRK3
NM_001012338.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.642

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

NTRK3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NTRK3	NM_001012338.3	MANE Select	c.2134-110T>A	intron	N/A	NP_001012338.1
NTRK3	NM_001375810.1		c.2134-110T>A	intron	N/A	NP_001362739.1
NTRK3	NM_001375811.1		c.2134-5417T>A	intron	N/A	NP_001362740.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.2134-110T>A	intron	N/A	ENSP00000485864.1
NTRK3	ENST00000557856.5	TSL:1	c.2110-5417T>A	intron	N/A	ENSP00000453959.1
NTRK3	ENST00000626019.2	TSL:5	c.2209-110T>A	intron	N/A	ENSP00000486784.1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151656

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

266480

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135612

African (AFR)

AF:

0.00

AC:

AN:

7422

American (AMR)

AF:

0.00

AC:

AN:

7094

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9192

East Asian (EAS)

AF:

0.00

AC:

AN:

22592

South Asian (SAS)

AF:

0.00

AC:

AN:

7666

European-Finnish (FIN)

AF:

0.00

AC:

AN:

20812

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1322

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

173408

Other (OTH)

AF:

0.00

AC:

AN:

16972

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151656

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74046

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10544

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67784

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

1542

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.64

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over