15-88125460-T-G

Variant names:

• chr15-88125460-T-G
• rs12911150
• NM_001012338.3:c.1396+811A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012338.3(NTRK3):​c.1396+811A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,348 control chromosomes in the GnomAD database, including 3,625 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 0.21 (3625 hom., cov: 30)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.274 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012338.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	NM_001012338.3	MANE Select	c.1396+811A>C		intron	N/A	NP_001012338.1	X5D2R1
	NTRK3	NM_001375810.1		c.1396+811A>C		intron	N/A	NP_001362739.1	Q16288-1
	NTRK3	NM_001375811.1		c.1396+811A>C		intron	N/A	NP_001362740.1	X5D7M5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NTRK3	ENST00000629765.3	TSL:1 MANE Select	c.1396+811A>C		intron	N/A	ENSP00000485864.1	Q16288-1
	NTRK3	ENST00000557856.5	TSL:1	c.1372+811A>C		intron	N/A	ENSP00000453959.1	Q16288-5
	NTRK3	ENST00000558676.5	TSL:1	c.1372+811A>C		intron	N/A	ENSP00000453511.1	H0YM90

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32299 AN: 151228 Hom.: 3622 Cov.: 30

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.213 AC: 32311 AN: 151348 Hom.: 3625 Cov.: 30 AF XY: 0.211 AC XY: 15565 AN XY: 73928

African (AFR) AF: 0.234 AC: 9653 AN: 41178

American (AMR) AF: 0.223 AC: 3367 AN: 15130

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 678 AN: 3466

East Asian (EAS) AF: 0.123 AC: 631 AN: 5110

South Asian (SAS) AF: 0.287 AC: 1375 AN: 4790

European-Finnish (FIN) AF: 0.161 AC: 1681 AN: 10464

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14235 AN: 67904

Other (OTH) AF: 0.201 AC: 423 AN: 2102

Alfa AF: 0.204 Hom.: 5410

Bravo AF: 0.215

Asia WGS AF: 0.242 AC: 842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.60
PhyloP100		0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12911150; hg19: chr15-88668691;