rs28565987

Variant names:

• chr15-88048299-C-A
• rs28565987
• NM_001012338.3:c.1397-15254G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-88048299-C-A
• chr15-88048299-C-G
• chr15-88048299-C-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001012338.3(NTRK3):​c.1397-15254G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 152,198 control chromosomes in the GnomAD database, including 723 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 0.094 (723 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 2 publications found

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	NM_001012338.3	MANE Select	c.1397-15254G>T		intron	N/A	NP_001012338.1
	NTRK3	NM_001375810.1		c.1397-15254G>T		intron	N/A	NP_001362739.1
	NTRK3	NM_001375811.1		c.1397-15254G>T		intron	N/A	NP_001362740.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.1397-15254G>T		intron	N/A	ENSP00000485864.1
	NTRK3	ENST00000557856.5	TSL:1	c.1373-15254G>T		intron	N/A	ENSP00000453959.1
	NTRK3	ENST00000558676.5	TSL:1	c.1373-15254G>T		intron	N/A	ENSP00000453511.1

Frequencies

GnomAD3 genomes AF: 0.0946 AC: 14381 AN: 152080 Hom.: 723 Cov.: 32

Gnomad AFR AF: 0.0632

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0841

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.0890

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

GnomAD4 genome AF: 0.0944 AC: 14374 AN: 152198 Hom.: 723 Cov.: 32 AF XY: 0.0932 AC XY: 6934 AN XY: 74388

African (AFR) AF: 0.0631 AC: 2619 AN: 41534

American (AMR) AF: 0.104 AC: 1595 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3472

East Asian (EAS) AF: 0.105 AC: 541 AN: 5170

South Asian (SAS) AF: 0.0952 AC: 458 AN: 4812

European-Finnish (FIN) AF: 0.0841 AC: 891 AN: 10594

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7635 AN: 68012

Other (OTH) AF: 0.0885 AC: 187 AN: 2112

Alfa AF: 0.101 Hom.: 1312

Bravo AF: 0.0937

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	21
DANN	Benign	0.77
PhyloP100		2.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs28565987; hg19: chr15-88591530;