rs1006046

chr15-87932935-A-Cchr15-87932935-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001012338.3(NTRK3):c.1889+77T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 1,475,410 control chromosomes in the GnomAD database, including 2,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.055 (273 hom., cov: 32)
  • Exomes 𝑓: 0.051 (1993 hom.)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.545

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 15-87932935-A-C is Benign according to our data. Variant chr15-87932935-A-C is described in ClinVar as [Benign]. Clinvar id is 1276265.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.1889+77T>G		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.1889+77T>G		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.0550 AC: 8368 AN: 152094 Hom.: 268 Cov.: 32

Gnomad AFR AF: 0.0779

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0691

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0343

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.0541

GnomAD4 exome AF: 0.0513 AC: 67876 AN: 1323198 Hom.: 1993 AF XY: 0.0515 AC XY: 34174 AN XY: 663372

Gnomad4 AFR exome AF: 0.0761

Gnomad4 AMR exome AF: 0.0340

Gnomad4 ASJ exome AF: 0.0622

Gnomad4 EAS exome AF: 0.000232

Gnomad4 SAS exome AF: 0.0414

Gnomad4 FIN exome AF: 0.0245

Gnomad4 NFE exome AF: 0.0552

Gnomad4 OTH exome AF: 0.0515

GnomAD4 genome AF: 0.0551 AC: 8392 AN: 152212 Hom.: 273 Cov.: 32 AF XY: 0.0522 AC XY: 3883 AN XY: 74430

Gnomad4 AFR AF: 0.0783

Gnomad4 AMR AF: 0.0445

Gnomad4 ASJ AF: 0.0691

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0341

Gnomad4 FIN AF: 0.0204

Gnomad4 NFE AF: 0.0538

Gnomad4 OTH AF: 0.0535

Alfa AF: 0.0560 Hom.: 349

Bravo AF: 0.0574

Asia WGS AF: 0.0210 AC: 73 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.63
Dann	Benign	0.73

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: rs1006046; hg19: chr15-88476166;