15-87876716-A-AAT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001012338.3(NTRK3):c.*218_*219insAT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 190,914 control chromosomes in the GnomAD database, including 554 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.083 (549 hom., cov: 29)
  • Exomes 𝑓: 0.097 (5 hom.)
• Consequence: NTRK3 NM_001012338.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.38

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 -10 ACMG points.

• BP6: Variant 15-87876716-A-AAT is Benign according to our data. Variant chr15-87876716-A-AAT is described in ClinVar as [Benign]. Clinvar id is 1285761.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.*218_*219insAT		3_prime_UTR_variant	20/20	ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.*218_*219insAT		3_prime_UTR_variant	20/20	1	NM_001012338.3
NTRK3	ENST00000394480.6	c.*218_*219insAT		3_prime_UTR_variant	19/19	5		P1
NTRK3	ENST00000357724.6			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0830 AC: 11841 AN: 142694 Hom.: 549 Cov.: 29

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.0638

Gnomad AMR AF: 0.0656

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0710

Gnomad FIN AF: 0.0737

Gnomad MID AF: 0.0993

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.0927

GnomAD4 exome AF: 0.0974 AC: 4695 AN: 48226 Hom.: 5 Cov.: 0 AF XY: 0.0998 AC XY: 2465 AN XY: 24700

Gnomad4 AFR exome AF: 0.0779

Gnomad4 AMR exome AF: 0.0740

Gnomad4 ASJ exome AF: 0.128

Gnomad4 EAS exome AF: 0.0461

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0727

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0958

GnomAD4 genome AF: 0.0829 AC: 11835 AN: 142688 Hom.: 549 Cov.: 29 AF XY: 0.0795 AC XY: 5505 AN XY: 69212

Gnomad4 AFR AF: 0.0487

Gnomad4 AMR AF: 0.0654

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0130

Gnomad4 SAS AF: 0.0703

Gnomad4 FIN AF: 0.0737

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.0922

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 20, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs147238996; hg19: chr15-88419947;