15-88118508-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1396+7763T>C		intron_variant	Intron 13 of 19	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1396+7763T>C		intron_variant	Intron 13 of 19	1	NM_001012338.3	ENSP00000485864.1

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

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.357

Alfa AF: 0.361 Hom.: 21666

Bravo AF: 0.367

Asia WGS AF: 0.296 AC: 1032 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.032
DANN	Benign	0.62

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: rs9806762; hg19: chr15-88661739;