rs28565987

chr15-88048299-C-Achr15-88048299-C-Gchr15-88048299-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.1397-15254G>T		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.1397-15254G>T		intron_variant		1	NM_001012338.3

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

Gnomad4 AFR AF: 0.0631

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0925

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0952

Gnomad4 FIN AF: 0.0841

Gnomad4 NFE AF: 0.112

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0719 Hom.: 127

Bravo AF: 0.0937

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
Cadd	Benign	21
Dann	Benign	0.77

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

LitVar

Other links and lift over

dbSNP: rs28565987; hg19: chr15-88591530;