dbSNP rs1560975: NTRK3:c.2334+38G>A (chr15-87880232-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001012338.3(NTRK3):c.2334+38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 1,612,112 control chromosomes in the GnomAD database, including 280,717 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.49 ( 20165 hom., cov: 31)

Exomes 𝑓: 0.59 ( 260552 hom. )

Consequence

NTRK3
NM_001012338.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.297

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 15-87880232-C-T is Benign according to our data. Variant chr15-87880232-C-T is described in ClinVar as Benign. ClinVar VariationId is 1249082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.605 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.2334+38G>A	intron	N/A	NP_001012338.1	X5D2R1
NTRK3	NM_001375810.1		c.2334+38G>A	intron	N/A	NP_001362739.1	Q16288-1
NTRK3	NM_001375811.1		c.2292+38G>A	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.2334+38G>A	intron	N/A	ENSP00000485864.1	Q16288-1
NTRK3	ENST00000557856.5	TSL:1	c.2268+38G>A	intron	N/A	ENSP00000453959.1	Q16288-5
NTRK3	ENST00000889753.1		c.2427+38G>A	intron	N/A	ENSP00000559812.1

Frequencies

GnomAD3 genomes

AF:

0.487

AC:

73877

AN:

151646

Hom.:

20158

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.496

Gnomad AMR

AF:

0.546

Gnomad ASJ

AF:

0.609

Gnomad EAS

AF:

0.602

Gnomad SAS

AF:

0.421

Gnomad FIN

AF:

0.589

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.511

GnomAD2 exomes

AF:

0.547

AC:

137465

AN:

251166

AF XY:

0.548

show subpopulations

Gnomad AFR exome

AF:

0.207

Gnomad AMR exome

AF:

0.544

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.598

Gnomad FIN exome

AF:

0.576

Gnomad NFE exome

AF:

0.611

Gnomad OTH exome

AF:

0.574

GnomAD4 exome

AF:

0.591

AC:

863300

AN:

1460348

Hom.:

260552

Cov.:

AF XY:

0.587

AC XY:

426416

AN XY:

726540

show subpopulations

African (AFR)

AF:

0.200

AC:

6702

AN:

33464

American (AMR)

AF:

0.546

AC:

24415

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

15793

AN:

26126

East Asian (EAS)

AF:

0.622

AC:

24700

AN:

39686

South Asian (SAS)

AF:

0.416

AC:

35856

AN:

86200

European-Finnish (FIN)

AF:

0.581

AC:

31019

AN:

53392

Middle Eastern (MID)

AF:

0.477

AC:

2614

AN:

5480

European-Non Finnish (NFE)

AF:

0.619

AC:

687819

AN:

1110960

Other (OTH)

AF:

0.570

AC:

34382

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

17408

34815

52223

69630

87038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18338

36676

55014

73352

91690

<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:

0.487

AC:

73890

AN:

151764

Hom.:

20165

Cov.:

AF XY:

0.486

AC XY:

36016

AN XY:

74166

show subpopulations

African (AFR)

AF:

0.219

AC:

9065

AN:

41388

American (AMR)

AF:

0.547

AC:

8345

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.609

AC:

2111

AN:

3466

East Asian (EAS)

AF:

0.602

AC:

3084

AN:

5126

South Asian (SAS)

AF:

0.420

AC:

2021

AN:

4812

European-Finnish (FIN)

AF:

0.589

AC:

6198

AN:

10520

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.610

AC:

41411

AN:

67886

Other (OTH)

AF:

0.507

AC:

1068

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1735

3470

5205

6940

8675

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<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:

0.562

Hom.:

69041

Bravo

AF:

0.477

Asia WGS

AF:

0.483

AC:

1684

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.7

(source)

DANN

Benign

0.44

PhyloP100

-0.30

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