15-88180481-T-G

Variant names:

• chr15-88180481-T-G
• rs1104918
• NM_001012338.3:c.395+2937A>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.395+2937A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 152,022 control chromosomes in the GnomAD database, including 4,595 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 0.24 (4595 hom., cov: 32)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.353
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.395+2937A>C		intron_variant	Intron 5 of 19	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765.3	c.395+2937A>C		intron_variant	Intron 5 of 19	1	NM_001012338.3	ENSP00000485864.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36427 AN: 151904 Hom.: 4592 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.240 AC: 36451 AN: 152022 Hom.: 4595 Cov.: 32 AF XY: 0.236 AC XY: 17558 AN XY: 74334

African (AFR) AF: 0.264 AC: 10942 AN: 41452

American (AMR) AF: 0.236 AC: 3608 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3470

East Asian (EAS) AF: 0.141 AC: 731 AN: 5170

South Asian (SAS) AF: 0.312 AC: 1501 AN: 4804

European-Finnish (FIN) AF: 0.172 AC: 1814 AN: 10560

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.242 AC: 16454 AN: 67972

Other (OTH) AF: 0.210 AC: 444 AN: 2112

Alfa AF: 0.234 Hom.: 7618

Bravo AF: 0.240

Asia WGS AF: 0.250 AC: 870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.38
DANN	Benign	0.39
PhyloP100		-0.35
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: rs1104918; hg19: chr15-88723712;