rs6496463

chr15-88145423-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.464+1912A>G		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.464+1912A>G		intron_variant		1	NM_001012338.3

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

Gnomad4 AFR AF: 0.771

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.533

Gnomad4 EAS AF: 0.497

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.481

Gnomad4 OTH AF: 0.517

Alfa AF: 0.509 Hom.: 4065

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

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: rs6496463; hg19: chr15-88688654;