dbSNP rs28521337: NTRK3:c.*1296G>C (chr15-87978049-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001007156.3(NTRK3):c.*1296G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 232,960 control chromosomes in the GnomAD database, including 45,227 homozygotes. 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 0.63 ( 31291 hom., cov: 33)

Exomes 𝑓: 0.57 ( 13936 hom. )

Consequence

NTRK3
NM_001007156.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.208

Publications

11 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.825 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007156.3. 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.1586-37296G>C	intron	N/A	NP_001012338.1	X5D2R1
NTRK3	NM_001007156.3		c.*1296G>C	3_prime_UTR	Exon 16 of 16	NP_001007157.1	Q16288-2
NTRK3	NM_001375813.1		c.*1296G>C	3_prime_UTR	Exon 14 of 14	NP_001362742.1	Q96CY4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NTRK3	ENST00000317501.9	TSL:1	c.*1296G>C	3_prime_UTR	Exon 16 of 16	ENSP00000318328.3	Q16288-2
NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.1586-37296G>C	intron	N/A	ENSP00000485864.1	Q16288-1
NTRK3	ENST00000557856.5	TSL:1	c.1562-37296G>C	intron	N/A	ENSP00000453959.1	Q16288-5

Frequencies

GnomAD3 genomes

AF:

0.625

AC:

95011

AN:

151986

Hom.:

31222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.832

Gnomad AMI

AF:

0.560

Gnomad AMR

AF:

0.605

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.803

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.533

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.521

Gnomad OTH

AF:

0.606

GnomAD4 exome

AF:

0.575

AC:

46489

AN:

80856

Hom.:

13936

Cov.:

AF XY:

0.572

AC XY:

21392

AN XY:

37366

show subpopulations

African (AFR)

AF:

0.844

AC:

3233

AN:

3832

American (AMR)

AF:

0.609

AC:

1495

AN:

2454

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

2392

AN:

5074

East Asian (EAS)

AF:

0.787

AC:

8925

AN:

11336

South Asian (SAS)

AF:

0.524

AC:

367

AN:

700

European-Finnish (FIN)

AF:

0.543

AC:

341

AN:

628

Middle Eastern (MID)

AF:

0.479

AC:

232

AN:

484

European-Non Finnish (NFE)

AF:

0.517

AC:

25699

AN:

49664

Other (OTH)

AF:

0.569

AC:

3805

AN:

6684

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

917

1834

2752

3669

4586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

252

378

504

630

<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:

0.625

AC:

95138

AN:

152104

Hom.:

31291

Cov.:

AF XY:

0.623

AC XY:

46292

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.832

AC:

34558

AN:

41540

American (AMR)

AF:

0.606

AC:

9257

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

1621

AN:

3470

East Asian (EAS)

AF:

0.803

AC:

4123

AN:

5134

South Asian (SAS)

AF:

0.536

AC:

2582

AN:

4816

European-Finnish (FIN)

AF:

0.533

AC:

5645

AN:

10584

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.521

AC:

35401

AN:

67970

Other (OTH)

AF:

0.607

AC:

1281

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1707

3414

5121

6828

8535

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.561

Hom.:

3098

Bravo

AF:

0.646

Asia WGS

AF:

0.676

AC:

2353

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

3.1

(source)

DANN

Benign

0.44

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(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

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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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over