dbSNP rs7180942: NTRK3:c.1205-2611A>G (chr15-88131345-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001012338.3(NTRK3):c.1205-2611A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,166 control chromosomes in the GnomAD database, including 24,581 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 0.55 ( 24581 hom., cov: 34)

Consequence

NTRK3
NM_001012338.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362

Publications

10 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=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 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.1205-2611A>G	intron	N/A	NP_001012338.1	X5D2R1
NTRK3	NM_001375810.1		c.1205-2611A>G	intron	N/A	NP_001362739.1	Q16288-1
NTRK3	NM_001375811.1		c.1205-2611A>G	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.1205-2611A>G	intron	N/A	ENSP00000485864.1	Q16288-1
NTRK3	ENST00000557856.5	TSL:1	c.1204+3756A>G	intron	N/A	ENSP00000453959.1	Q16288-5
NTRK3	ENST00000558676.5	TSL:1	c.1204+3756A>G	intron	N/A	ENSP00000453511.1	H0YM90

Frequencies

GnomAD3 genomes

AF:

0.550

AC:

83586

AN:

152048

Hom.:

24535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.778

Gnomad AMI

AF:

0.471

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.472

Gnomad FIN

AF:

0.393

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.480

Gnomad OTH

AF:

0.519

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

GnomAD4 genome

AF:

0.550

AC:

83697

AN:

152166

Hom.:

24581

Cov.:

AF XY:

0.541

AC XY:

40264

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.778

AC:

32312

AN:

41524

American (AMR)

AF:

0.443

AC:

6766

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.546

AC:

1895

AN:

3472

East Asian (EAS)

AF:

0.370

AC:

1915

AN:

5172

South Asian (SAS)

AF:

0.473

AC:

2281

AN:

4824

European-Finnish (FIN)

AF:

0.393

AC:

4154

AN:

10572

Middle Eastern (MID)

AF:

0.565

AC:

166

AN:

294

European-Non Finnish (NFE)

AF:

0.480

AC:

32673

AN:

68000

Other (OTH)

AF:

0.523

AC:

1105

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1831

3663

5494

7326

9157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.526

Hom.:

2852

Bravo

AF:

0.560

Asia WGS

AF:

0.458

AC:

1595

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.8

(source)

DANN

Benign

0.28

PhyloP100

0.36

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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