chr15-88059610-T-C

Variant names:

• chr15-88059610-T-C
• rs3825885
• NM_001012338.3:c.1397-26565A>G

Variant summary

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

The NM_001012338.3(NTRK3):​c.1397-26565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.317 in 152,050 control chromosomes in the GnomAD database, including 7,757 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 0.32 (7757 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1397-26565A>G		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.1397-26565A>G		intron_variant	Intron 13 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48174 AN: 151932 Hom.: 7729 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.200

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.319

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.317 AC: 48265 AN: 152050 Hom.: 7757 Cov.: 32 AF XY: 0.318 AC XY: 23612 AN XY: 74348

African (AFR) AF: 0.345 AC: 14305 AN: 41450

American (AMR) AF: 0.269 AC: 4106 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3468

East Asian (EAS) AF: 0.312 AC: 1609 AN: 5160

South Asian (SAS) AF: 0.278 AC: 1338 AN: 4812

European-Finnish (FIN) AF: 0.306 AC: 3241 AN: 10590

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.319 AC: 21673 AN: 67972

Other (OTH) AF: 0.296 AC: 626 AN: 2114

Alfa AF: 0.313 Hom.: 31046

Bravo AF: 0.313

Asia WGS AF: 0.320 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.34
PhyloP100		0.15
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: rs3825885; hg19: chr15-88602841;