chr15-87928939-A-G

Position:

• chr15-87928939-A-G

Variant summary

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

The ENST00000558676(NTRK3):​c.*243T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 604,626 control chromosomes in the GnomAD database, including 10,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2081 hom., cov: 32)
  • Exomes 𝑓: 0.19 (8284 hom.)
• Consequence: NTRK3 ENST00000558676 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31

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=-0.67).
• BP6: Variant 15-87928939-A-G is Benign according to our data. Variant chr15-87928939-A-G is described in ClinVar as [Benign]. Clinvar id is 1284241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.2133+252T>C		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.2133+252T>C		intron_variant		1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23829 AN: 152106 Hom.: 2079 Cov.: 32

Gnomad AFR AF: 0.108

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.187 AC: 84427 AN: 452400 Hom.: 8284 Cov.: 4 AF XY: 0.191 AC XY: 45551 AN XY: 238362

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.109

Gnomad4 ASJ exome AF: 0.175

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.248

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.197

Gnomad4 OTH exome AF: 0.181

GnomAD4 genome AF: 0.157 AC: 23857 AN: 152226 Hom.: 2081 Cov.: 32 AF XY: 0.154 AC XY: 11469 AN XY: 74430

Gnomad4 AFR AF: 0.108

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.153

Alfa AF: 0.177 Hom.: 956

Bravo AF: 0.154

Asia WGS AF: 0.204 AC: 706 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	Nov 12, 2018	- -
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	-0.67
CADD	Benign	0.73
DANN	Benign	0.89

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: rs879131; hg19: chr15-88472170;