15-88255577-CA-CAAA

Variant names:

• chr15-88255577-C-CAA
• rs142609804
• NM_001012338.3:c.248+327_248+328dupTT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001012338.3(NTRK3):​c.248+327_248+328dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000734 in 149,916 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 0.000073 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 11 AD gene.

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+327_248+328dupTT		intron	N/A	NP_001012338.1	X5D2R1
	NTRK3	NM_001375810.1		c.248+327_248+328dupTT		intron	N/A	NP_001362739.1	Q16288-1
	NTRK3	NM_001375811.1		c.248+327_248+328dupTT		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+328_248+329insTT		intron	N/A	ENSP00000485864.1	Q16288-1
	NTRK3	ENST00000557856.5	TSL:1	c.248+328_248+329insTT		intron	N/A	ENSP00000453959.1	Q16288-5
	NTRK3	ENST00000558676.5	TSL:1	c.248+328_248+329insTT		intron	N/A	ENSP00000453511.1	H0YM90

Frequencies

GnomAD3 genomes AF: 0.0000734 AC: 11 AN: 149916 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000133

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00118

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000297

Gnomad OTH AF: 0.000486

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

GnomAD4 genome AF: 0.0000734 AC: 11 AN: 149916 Hom.: 0 Cov.: 31 AF XY: 0.0000822 AC XY: 6 AN XY: 73028

African (AFR) AF: 0.00 AC: 0 AN: 40866

American (AMR) AF: 0.000133 AC: 2 AN: 15054

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

East Asian (EAS) AF: 0.00118 AC: 6 AN: 5084

South Asian (SAS) AF: 0.00 AC: 0 AN: 4724

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67322

Other (OTH) AF: 0.000486 AC: 1 AN: 2058

Alfa AF: 0.00 Hom.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs142609804; hg19: chr15-88798808;