15-87933455-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001012338.3(NTRK3):c.1717-271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 152,330 control chromosomes in the GnomAD database, including 44 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.019 (44 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0760

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=-0.87).
• BP6: Variant 15-87933455-C-T is Benign according to our data. Variant chr15-87933455-C-T is described in ClinVar as [Benign]. Clinvar id is 1275495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0191 (2909/152330) while in subpopulation EAS AF= 0.0321 (166/5166). AF 95% confidence interval is 0.0281. There are 44 homozygotes in gnomad4. There are 1576 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2909 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.1717-271G>A		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.1717-271G>A		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.0191 AC: 2909 AN: 152212 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.00330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0173

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.0323

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0683

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0124

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

GnomAD4 genome AF: 0.0191 AC: 2909 AN: 152330 Hom.: 44 Cov.: 33 AF XY: 0.0212 AC XY: 1576 AN XY: 74488

Gnomad4 AFR AF: 0.00329

Gnomad4 AMR AF: 0.0172

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.0321

Gnomad4 SAS AF: 0.00581

Gnomad4 FIN AF: 0.0683

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0220 Hom.: 2

Bravo AF: 0.0145

Asia WGS AF: 0.0190 AC: 65 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 21, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.1
Dann	Benign	0.64

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: rs116932643; hg19: chr15-88476686;