rs1017412

Positions:

• chr15-87868912-G-A
• chr15-87868912-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012338.3(NTRK3):​c.*8023C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 225,494 control chromosomes in the GnomAD database, including 49,206 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (32175 hom., cov: 33)
  • Exomes 𝑓: 0.68 (17031 hom.)
• Consequence: NTRK3 NM_001012338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.*8023C>T		3_prime_UTR_variant	20/20	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765	c.*8023C>T		3_prime_UTR_variant	20/20	1	NM_001012338.3	ENSP00000485864.1
NTRK3	ENST00000394480	c.*8023C>T		3_prime_UTR_variant	19/19	5		ENSP00000377990.1

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98550 AN: 152010 Hom.: 32150 Cov.: 33

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.660

GnomAD4 exome AF: 0.680 AC: 49882 AN: 73368 Hom.: 17031 Cov.: 0 AF XY: 0.683 AC XY: 23207 AN XY: 33974

Gnomad4 AFR exome AF: 0.598

Gnomad4 AMR exome AF: 0.629

Gnomad4 ASJ exome AF: 0.688

Gnomad4 EAS exome AF: 0.731

Gnomad4 SAS exome AF: 0.596

Gnomad4 FIN exome AF: 0.672

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.664

GnomAD4 genome AF: 0.648 AC: 98624 AN: 152126 Hom.: 32175 Cov.: 33 AF XY: 0.649 AC XY: 48238 AN XY: 74350

Gnomad4 AFR AF: 0.588

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.685

Gnomad4 EAS AF: 0.668

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.656

Alfa AF: 0.646 Hom.: 3802

Bravo AF: 0.646

Asia WGS AF: 0.634 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.60

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: rs1017412; hg19: chr15-88412143;