rs3825882

Positions:

• chr15-88126151-G-C
• chr15-88126151-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001012338.3(NTRK3):​c.1396+120C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 753,346 control chromosomes in the GnomAD database, including 99,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (24016 hom., cov: 32)
  • Exomes 𝑓: 0.49 (75189 hom.)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.595

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-88126151-G-C is Benign according to our data. Variant chr15-88126151-G-C is described in ClinVar as [Benign]. Clinvar id is 1277211.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1396+120C>G		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1396+120C>G		intron_variant		1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83032 AN: 151884 Hom.: 23972 Cov.: 32

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.494 AC: 296968 AN: 601344 Hom.: 75189 AF XY: 0.500 AC XY: 161044 AN XY: 322130

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.403

Gnomad4 ASJ exome AF: 0.568

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.408

Gnomad4 NFE exome AF: 0.489

Gnomad4 OTH exome AF: 0.511

GnomAD4 genome AF: 0.547 AC: 83133 AN: 152002 Hom.: 24016 Cov.: 32 AF XY: 0.540 AC XY: 40154 AN XY: 74294

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.366

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.509

Alfa AF: 0.384 Hom.: 1039

Bravo AF: 0.552

Asia WGS AF: 0.527 AC: 1836 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.35

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: rs3825882; hg19: chr15-88669382; COSMIC: COSV58150661;