15-87925700-T-C

Position:

• chr15-87925700-T-C

Variant summary

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

The NM_001012338.3(NTRK3):​c.2133+3491A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 186,064 control chromosomes in the GnomAD database, including 1,851 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 0.13 (1476 hom., cov: 33)
  • Exomes 𝑓: 0.15 (375 hom.)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.2133+3491A>G		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.2133+3491A>G		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19856 AN: 152148 Hom.: 1473 Cov.: 33

Gnomad AFR AF: 0.0907

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.0896

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.148 AC: 5008 AN: 33798 Hom.: 375 Cov.: 0 AF XY: 0.145 AC XY: 2259 AN XY: 15572

Gnomad4 AFR exome AF: 0.0789

Gnomad4 AMR exome AF: 0.0931

Gnomad4 ASJ exome AF: 0.139

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.262

Gnomad4 FIN exome AF: 0.0556

Gnomad4 NFE exome AF: 0.156

Gnomad4 OTH exome AF: 0.147

GnomAD4 genome AF: 0.131 AC: 19878 AN: 152266 Hom.: 1476 Cov.: 33 AF XY: 0.130 AC XY: 9689 AN XY: 74466

Gnomad4 AFR AF: 0.0909

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.133

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.0896

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.132

Alfa AF: 0.149 Hom.: 2538

Bravo AF: 0.127

Asia WGS AF: 0.192 AC: 666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.69

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: rs1078163; hg19: chr15-88468931;