15-88118508-A-G

Variant names:

• chr15-88118508-A-G
• rs9806762
• NM_001012338.3:c.1396+7763T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012338.3(NTRK3):​c.1396+7763T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,138 control chromosomes in the GnomAD database, including 10,559 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 0.37 (10559 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.434 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	NM_001012338.3	MANE Select	c.1396+7763T>C		intron	N/A	NP_001012338.1
	NTRK3	NM_001375810.1		c.1396+7763T>C		intron	N/A	NP_001362739.1
	NTRK3	NM_001375811.1		c.1396+7763T>C		intron	N/A	NP_001362740.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.1396+7763T>C		intron	N/A	ENSP00000485864.1
	NTRK3	ENST00000557856.5	TSL:1	c.1372+7763T>C		intron	N/A	ENSP00000453959.1
	NTRK3	ENST00000558676.5	TSL:1	c.1372+7763T>C		intron	N/A	ENSP00000453511.1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55661 AN: 152020 Hom.: 10543 Cov.: 33

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.366 AC: 55714 AN: 152138 Hom.: 10559 Cov.: 33 AF XY: 0.360 AC XY: 26806 AN XY: 74372

African (AFR) AF: 0.439 AC: 18226 AN: 41512

American (AMR) AF: 0.257 AC: 3926 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1534 AN: 3468

East Asian (EAS) AF: 0.252 AC: 1306 AN: 5186

South Asian (SAS) AF: 0.330 AC: 1593 AN: 4820

European-Finnish (FIN) AF: 0.301 AC: 3179 AN: 10572

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.364 AC: 24713 AN: 67984

Other (OTH) AF: 0.357 AC: 753 AN: 2108

Alfa AF: 0.364 Hom.: 45063

Bravo AF: 0.367

Asia WGS AF: 0.296 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.032
DANN	Benign	0.62
PhyloP100		-1.4
Mutation Taster		=100/0	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: rs9806762; hg19: chr15-88661739;