rs7180942

Positions:

• chr15-88131345-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.1205-2611A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 152,166 control chromosomes in the GnomAD database, including 24,581 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 0.55 (24581 hom., cov: 34)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.1205-2611A>G		intron_variant		ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.1205-2611A>G		intron_variant		1	NM_001012338.3	ENSP00000485864

Frequencies

GnomAD3 genomes AF: 0.550 AC: 83586 AN: 152048 Hom.: 24535 Cov.: 34

Gnomad AFR AF: 0.778

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.546

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.472

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.519

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

GnomAD4 genome AF: 0.550 AC: 83697 AN: 152166 Hom.: 24581 Cov.: 34 AF XY: 0.541 AC XY: 40264 AN XY: 74364

Gnomad4 AFR AF: 0.778

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.546

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.473

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.480

Gnomad4 OTH AF: 0.523

Alfa AF: 0.517 Hom.: 2635

Bravo AF: 0.560

Asia WGS AF: 0.458 AC: 1595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.8
DANN	Benign	0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs7180942; hg19: chr15-88674576;