Genetic Variant NTRK3:c.248+328dupT (chr15-88255577-C-CA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001012338.3(NTRK3):c.248+328dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0814 in 149,972 control chromosomes in the GnomAD database, including 633 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.081 ( 633 hom., cov: 31)

Consequence

NTRK3
NM_001012338.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.493

Publications

0 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 links:

NTRK3-AS1 (HGNC:27532): (NTRK3 antisense RNA 1)

NTRK3-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 15-88255577-C-CA is Benign according to our data. Variant chr15-88255577-C-CA is described in ClinVar as Benign. ClinVar VariationId is 1264869.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.

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	UniProt
NTRK3	NM_001012338.3	MANE Select	c.248+328dupT	intron	N/A	NP_001012338.1	X5D2R1
NTRK3	NM_001375810.1		c.248+328dupT	intron	N/A	NP_001362739.1	Q16288-1
NTRK3	NM_001375811.1		c.248+328dupT	intron	N/A	NP_001362740.1	X5D7M5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.248+328_248+329insT	intron	N/A	ENSP00000485864.1	Q16288-1
NTRK3	ENST00000557856.5	TSL:1	c.248+328_248+329insT	intron	N/A	ENSP00000453959.1	Q16288-5
NTRK3	ENST00000558676.5	TSL:1	c.248+328_248+329insT	intron	N/A	ENSP00000453511.1	H0YM90

Frequencies

GnomAD3 genomes

AF:

0.0815

AC:

12220

AN:

149858

Hom.:

635

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0276

Gnomad AMI

AF:

0.0122

Gnomad AMR

AF:

0.0682

Gnomad ASJ

AF:

0.0945

Gnomad EAS

AF:

0.136

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.0936

Gnomad MID

AF:

0.0609

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0782

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0814

AC:

12215

AN:

149972

Hom.:

633

Cov.:

AF XY:

0.0794

AC XY:

5809

AN XY:

73120

show subpopulations

African (AFR)

AF:

0.0275

AC:

1126

AN:

40974

American (AMR)

AF:

0.0680

AC:

1025

AN:

15068

Ashkenazi Jewish (ASJ)

AF:

0.0945

AC:

327

AN:

3460

East Asian (EAS)

AF:

0.136

AC:

689

AN:

5068

South Asian (SAS)

AF:

0.103

AC:

488

AN:

4718

European-Finnish (FIN)

AF:

0.0936

AC:

947

AN:

10120

Middle Eastern (MID)

AF:

0.0621

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.110

AC:

7420

AN:

67290

Other (OTH)

AF:

0.0788

AC:

164

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

526

1051

1577

2102

2628

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0270

Hom.:

Bravo

AF:

0.0748

Asia WGS

AF:

0.135

AC:

467

AN:

3476

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.49

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over