chr15-88145423-T-C

Variant names:

• chr15-88145423-T-C
• rs6496463
• NM_001012338.3:c.464+1912A>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.464+1912A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.551 in 151,924 control chromosomes in the GnomAD database, including 24,521 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 0.55 (24521 hom., cov: 31)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.464+1912A>G		intron_variant	Intron 6 of 19	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.464+1912A>G		intron_variant	Intron 6 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83588 AN: 151806 Hom.: 24466 Cov.: 31

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.533

Gnomad EAS AF: 0.497

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.513

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

GnomAD4 genome AF: 0.551 AC: 83698 AN: 151924 Hom.: 24521 Cov.: 31 AF XY: 0.543 AC XY: 40310 AN XY: 74258

African (AFR) AF: 0.771 AC: 31935 AN: 41440

American (AMR) AF: 0.432 AC: 6599 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.533 AC: 1849 AN: 3472

East Asian (EAS) AF: 0.497 AC: 2565 AN: 5158

South Asian (SAS) AF: 0.475 AC: 2287 AN: 4812

European-Finnish (FIN) AF: 0.393 AC: 4146 AN: 10552

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32680 AN: 67914

Other (OTH) AF: 0.517 AC: 1087 AN: 2102

Alfa AF: 0.515 Hom.: 4288

Bravo AF: 0.560

Asia WGS AF: 0.518 AC: 1804 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	8.0
DANN	Benign	0.63
PhyloP100		0.17
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: rs6496463; hg19: chr15-88688654;