rs11073758

Variant names:

• chr15-88005887-A-G
• rs11073758
• NM_001012338.3:c.1585+26970T>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.1585+26970T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 152,032 control chromosomes in the GnomAD database, including 20,533 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 0.50 (20533 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.549
• Publications: 1 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 (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1585+26970T>C		intron_variant	Intron 14 of 19	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1585+26970T>C		intron_variant	Intron 14 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.504 AC: 76605 AN: 151914 Hom.: 20489 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.504 AC: 76694 AN: 152032 Hom.: 20533 Cov.: 32 AF XY: 0.498 AC XY: 37040 AN XY: 74314

African (AFR) AF: 0.687 AC: 28495 AN: 41454

American (AMR) AF: 0.446 AC: 6805 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1886 AN: 3468

East Asian (EAS) AF: 0.219 AC: 1131 AN: 5166

South Asian (SAS) AF: 0.491 AC: 2357 AN: 4804

European-Finnish (FIN) AF: 0.363 AC: 3847 AN: 10588

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30728 AN: 67968

Other (OTH) AF: 0.485 AC: 1024 AN: 2112

Alfa AF: 0.465 Hom.: 14645

Bravo AF: 0.515

Asia WGS AF: 0.402 AC: 1399 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	0.17
DANN	Benign	0.36
PhyloP100		-0.55
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: rs11073758; hg19: chr15-88549118;