15-87885471-C-A

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.2175+223G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 151,496 control chromosomes in the GnomAD database, including 22,698 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (22698 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.488

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=-0.93).
• BP6: Variant 15-87885471-C-A is Benign according to our data. Variant chr15-87885471-C-A is described in ClinVar as [Benign]. Clinvar id is 1275729.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.2175+223G>T		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.2175+223G>T		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79186 AN: 151378 Hom.: 22692 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.477

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.639

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.536

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

GnomAD4 genome AF: 0.523 AC: 79202 AN: 151496 Hom.: 22698 Cov.: 32 AF XY: 0.523 AC XY: 38695 AN XY: 74052

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.639

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.532

Alfa AF: 0.617 Hom.: 45435

Bravo AF: 0.511

Asia WGS AF: 0.513 AC: 1781 AN: 3466

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

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	9.0
Dann	Benign	0.46

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: rs2117655; hg19: chr15-88428702; COSMIC: COSV62296137;