chr15-88255581-A-T

Variant names:

• chr15-88255581-A-T
• rs59628990
• NM_001012338.3:c.248+325T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001012338.3(NTRK3):​c.248+325T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,022 control chromosomes in the GnomAD database, including 2,261 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.15 (2261 hom., cov: 31)
• Consequence: NTRK3 NM_001012338.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.75
• 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 15-88255581-A-T is Benign according to our data. Variant chr15-88255581-A-T is described in ClinVar as Benign. ClinVar VariationId is 1234989.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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.248+325T>A		intron	N/A	NP_001012338.1	X5D2R1
	NTRK3	NM_001375810.1		c.248+325T>A		intron	N/A	NP_001362739.1	Q16288-1
	NTRK3	NM_001375811.1		c.248+325T>A		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+325T>A		intron	N/A	ENSP00000485864.1	Q16288-1
	NTRK3	ENST00000557856.5	TSL:1	c.248+325T>A		intron	N/A	ENSP00000453959.1	Q16288-5
	NTRK3	ENST00000558676.5	TSL:1	c.248+325T>A		intron	N/A	ENSP00000453511.1	H0YM90

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23243 AN: 151904 Hom.: 2255 Cov.: 31

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.00892

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.128

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.153 AC: 23279 AN: 152022 Hom.: 2261 Cov.: 31 AF XY: 0.153 AC XY: 11366 AN XY: 74330

African (AFR) AF: 0.266 AC: 11045 AN: 41460

American (AMR) AF: 0.154 AC: 2359 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 580 AN: 3472

East Asian (EAS) AF: 0.00855 AC: 44 AN: 5146

South Asian (SAS) AF: 0.127 AC: 612 AN: 4818

European-Finnish (FIN) AF: 0.128 AC: 1355 AN: 10572

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6878 AN: 67946

Other (OTH) AF: 0.150 AC: 317 AN: 2112

Alfa AF: 0.136 Hom.: 197

Bravo AF: 0.160

Asia WGS AF: 0.103 AC: 358 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.7
DANN	Benign	0.57
PhyloP100		1.7
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: rs59628990; hg19: chr15-88798812;