rs142609804

Variant names:

• chr15-88255577-CA-C
• rs142609804
• NM_001012338.3:c.248+328delT

Your query was ambiguous. Multiple possible variants found:

• chr15-88255577-CA-C
• chr15-88255577-CA-CAA
• chr15-88255577-CA-CAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001012338.3(NTRK3):​c.248+328delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 150,032 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 31)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493
• Publications: 0 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-AS1 (HGNC:27532): (NTRK3 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.248+328delT		intron	N/A	NP_001012338.1	X5D2R1
	NTRK3	NM_001375810.1		c.248+328delT		intron	N/A	NP_001362739.1	Q16288-1
	NTRK3	NM_001375811.1		c.248+328delT		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.248+328delT		intron	N/A	ENSP00000485864.1	Q16288-1
	NTRK3	ENST00000557856.5	TSL:1	c.248+328delT		intron	N/A	ENSP00000453959.1	Q16288-5
	NTRK3	ENST00000558676.5	TSL:1	c.248+328delT		intron	N/A	ENSP00000453511.1	H0YM90

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 149918 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000245

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000212

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150032 Hom.: 0 Cov.: 31 AF XY: 0.0000273 AC XY: 2 AN XY: 73154

African (AFR) AF: 0.0000244 AC: 1 AN: 40988

American (AMR) AF: 0.00 AC: 0 AN: 15074

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5070

South Asian (SAS) AF: 0.000212 AC: 1 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10132

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67314

Other (OTH) AF: 0.00 AC: 0 AN: 2080

Alfa AF: 0.00 Hom.: 26

Bravo AF: 0.0000264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

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: rs142609804; hg19: chr15-88798808;