rs200822610

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001012338.3(NTRK3):c.61G>T(p.Val21Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000311 in 1,612,052 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

NTRK3
NM_001012338.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.577

Publications

10 publications found

Variant links:

COSMIC-nc: COSV58110608

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.008988023).

BP6

Variant 15-88256093-C-A is Benign according to our data. Variant chr15-88256093-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 719029.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 43 AD gene.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
NTRK3	NM_001012338.3	MANE Select	c.61G>T	p.Val21Phe	missense	Exon 3 of 20	NP_001012338.1	X5D2R1
NTRK3	NM_001375810.1		c.61G>T	p.Val21Phe	missense	Exon 1 of 18	NP_001362739.1	Q16288-1
NTRK3	NM_001375811.1		c.61G>T	p.Val21Phe	missense	Exon 1 of 17	NP_001362740.1	X5D7M5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.61G>T	p.Val21Phe	missense	Exon 3 of 20	ENSP00000485864.1	Q16288-1
NTRK3	ENST00000557856.5	TSL:1	c.61G>T	p.Val21Phe	missense	Exon 1 of 16	ENSP00000453959.1	Q16288-5
NTRK3	ENST00000558676.5	TSL:1	c.61G>T	p.Val21Phe	missense	Exon 1 of 14	ENSP00000453511.1	H0YM90

Frequencies

GnomAD3 genomes

AF:

0.000291

AC:

AN:

151012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000244

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00507

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.000474

AC:

119

AN:

251106

AF XY:

0.000434

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00621

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000314

AC:

459

AN:

1460926

Hom.:

Cov.:

AF XY:

0.000314

AC XY:

228

AN XY:

726774

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33452

American (AMR)

AF:

0.0000224

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00975

AC:

387

AN:

39674

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000360

AC:

AN:

1111428

Other (OTH)

AF:

0.00108

AC:

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

110

138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000285

AC:

AN:

151126

Hom.:

Cov.:

AF XY:

0.000176

AC XY:

AN XY:

73808

show subpopulations

African (AFR)

AF:

0.0000243

AC:

AN:

41146

American (AMR)

AF:

0.00105

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00508

AC:

AN:

5118

South Asian (SAS)

AF:

0.00

AC:

AN:

4750

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67758

Other (OTH)

AF:

0.00

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000375

Hom.:

Bravo

AF:

0.000276

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.00491

AC:

AN:

3476

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

NTRK3-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.33

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.83

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.0090

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.34

PhyloP100

0.58

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.41

REVEL

Benign

0.23

Sift

Benign

0.082

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.32

MVP

0.58

MPC

0.60

ClinPred

0.036

GERP RS

1.2

PromoterAI

-0.062

Neutral

(source)

Varity_R

0.095

gMVP

0.53

Mutation Taster

=70/30

polymorphism

(source)

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over