rs1834573

Variant names:

• chr15-88126882-T-A
• rs1834573
• NM_001012338.3:c.1293+280A>T

Your query was ambiguous. Multiple possible variants found:

• chr15-88126882-T-A
• chr15-88126882-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001012338.3(NTRK3):​c.1293+280A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 151,994 control chromosomes in the GnomAD database, including 8,761 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (8761 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.343
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-88126882-T-A is Benign according to our data. Variant chr15-88126882-T-A is described in ClinVar as [Benign]. Clinvar id is 1295969.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.454 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1293+280A>T		intron_variant	Intron 12 of 19	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1293+280A>T		intron_variant	Intron 12 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.329 AC: 50010 AN: 151876 Hom.: 8739 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.317

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

GnomAD4 genome AF: 0.329 AC: 50072 AN: 151994 Hom.: 8761 Cov.: 32 AF XY: 0.325 AC XY: 24132 AN XY: 74296

African (AFR) AF: 0.459 AC: 19016 AN: 41418

American (AMR) AF: 0.219 AC: 3348 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1342 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1207 AN: 5162

South Asian (SAS) AF: 0.313 AC: 1505 AN: 4814

European-Finnish (FIN) AF: 0.249 AC: 2627 AN: 10570

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20060 AN: 67958

Other (OTH) AF: 0.320 AC: 676 AN: 2112

Alfa AF: 0.169 Hom.: 294

Bravo AF: 0.333

Asia WGS AF: 0.279 AC: 973 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.054
DANN	Benign	0.65
PhyloP100		-0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1834573; hg19: chr15-88670113;