15-88081390-C-G

Variant names:

• chr15-88081390-C-G
• rs1870736
• NM_001012338.3:c.1396+44881G>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+44881G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,998 control chromosomes in the GnomAD database, including 10,412 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 0.36 (10412 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.487
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1396+44881G>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+44881G>C		intron_variant	Intron 13 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55224 AN: 151880 Hom.: 10402 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.355

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.364 AC: 55265 AN: 151998 Hom.: 10412 Cov.: 32 AF XY: 0.359 AC XY: 26623 AN XY: 74262

African (AFR) AF: 0.297 AC: 12303 AN: 41468

American (AMR) AF: 0.317 AC: 4849 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1514 AN: 3470

East Asian (EAS) AF: 0.263 AC: 1355 AN: 5152

South Asian (SAS) AF: 0.370 AC: 1785 AN: 4818

European-Finnish (FIN) AF: 0.355 AC: 3748 AN: 10546

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28609 AN: 67940

Other (OTH) AF: 0.359 AC: 756 AN: 2106

Alfa AF: 0.254 Hom.: 629

Bravo AF: 0.356

Asia WGS AF: 0.325 AC: 1131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.054
DANN	Benign	0.42
PhyloP100		-0.49
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: rs1870736; hg19: chr15-88624621;