rs8042990

chr15-88188222-G-Cchr15-88188222-G-T

Variant summary

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

The NM_001012338.3(NTRK3):c.249-3923C>G 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 152,150 control chromosomes in the GnomAD database, including 8,479 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 0.33 (8479 hom., cov: 33)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.249-3923C>G		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.249-3923C>G		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49967 AN: 152032 Hom.: 8464 Cov.: 33

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.329 AC: 50024 AN: 152150 Hom.: 8479 Cov.: 33 AF XY: 0.327 AC XY: 24337 AN XY: 74372

Gnomad4 AFR AF: 0.409

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.311

Alfa AF: 0.180 Hom.: 356

Bravo AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.16
Dann	Benign	0.44

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: rs8042990; hg19: chr15-88731453;