15-87885910-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001012338.3(NTRK3):c.2134-175T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,002 control chromosomes in the GnomAD database, including 1,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1225 hom., cov: 31)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.02

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=-0.25).
• BP6: Variant 15-87885910-A-G is Benign according to our data. Variant chr15-87885910-A-G is described in ClinVar as [Benign]. Clinvar id is 1260811.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NTRK3	NM_001012338.3	c.2134-175T>C		intron_variant		ENST00000629765.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NTRK3	ENST00000629765.3	c.2134-175T>C		intron_variant		1	NM_001012338.3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16926 AN: 151884 Hom.: 1221 Cov.: 31

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.0707

Gnomad ASJ AF: 0.0704

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.137

Gnomad FIN AF: 0.0511

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0807

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.112 AC: 16950 AN: 152002 Hom.: 1225 Cov.: 31 AF XY: 0.110 AC XY: 8210 AN XY: 74332

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.0706

Gnomad4 ASJ AF: 0.0704

Gnomad4 EAS AF: 0.0587

Gnomad4 SAS AF: 0.137

Gnomad4 FIN AF: 0.0511

Gnomad4 NFE AF: 0.0807

Gnomad4 OTH AF: 0.119

Alfa AF: 0.100 Hom.: 229

Bravo AF: 0.116

Asia WGS AF: 0.113 AC: 391 AN: 3472

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 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
Cadd	Benign	17
Dann	Benign	0.88

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: rs55868433; hg19: chr15-88429141;