rs1017412

Variant names:

• chr15-87868912-G-A
• rs1017412
• NM_001012338.3:c.*8023C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-87868912-G-A
• chr15-87868912-G-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.*8023C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 225,494 control chromosomes in the GnomAD database, including 49,206 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 0.65 (32175 hom., cov: 33)
  • Exomes 𝑓: 0.68 (17031 hom.)
• Consequence: NTRK3 NM_001012338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.346
• Publications: 9 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 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.*8023C>T		3_prime_UTR	Exon 20 of 20	NP_001012338.1	X5D2R1
	NTRK3	NM_001375810.1		c.*8023C>T		3_prime_UTR	Exon 18 of 18	NP_001362739.1	Q16288-1
	NTRK3	NM_001375811.1		c.*8023C>T		3_prime_UTR	Exon 17 of 17	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.*8023C>T		3_prime_UTR	Exon 20 of 20	ENSP00000485864.1	Q16288-1
	NTRK3	ENST00000394480.6	TSL:5	c.*8023C>T		3_prime_UTR	Exon 19 of 19	ENSP00000377990.1	Q16288-3

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98550 AN: 152010 Hom.: 32150 Cov.: 33

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.685

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.574

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.660

GnomAD4 exome AF: 0.680 AC: 49882 AN: 73368 Hom.: 17031 Cov.: 0 AF XY: 0.683 AC XY: 23207 AN XY: 33974

African (AFR) AF: 0.598 AC: 2098 AN: 3510

American (AMR) AF: 0.629 AC: 1372 AN: 2180

Ashkenazi Jewish (ASJ) AF: 0.688 AC: 3251 AN: 4726

East Asian (EAS) AF: 0.731 AC: 7699 AN: 10536

South Asian (SAS) AF: 0.596 AC: 384 AN: 644

European-Finnish (FIN) AF: 0.672 AC: 39 AN: 58

Middle Eastern (MID) AF: 0.621 AC: 278 AN: 448

European-Non Finnish (NFE) AF: 0.680 AC: 30688 AN: 45132

Other (OTH) AF: 0.664 AC: 4073 AN: 6134

GnomAD4 genome AF: 0.648 AC: 98624 AN: 152126 Hom.: 32175 Cov.: 33 AF XY: 0.649 AC XY: 48238 AN XY: 74350

African (AFR) AF: 0.588 AC: 24388 AN: 41504

American (AMR) AF: 0.650 AC: 9941 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.685 AC: 2372 AN: 3464

East Asian (EAS) AF: 0.668 AC: 3445 AN: 5156

South Asian (SAS) AF: 0.572 AC: 2758 AN: 4820

European-Finnish (FIN) AF: 0.690 AC: 7303 AN: 10578

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.680 AC: 46262 AN: 68000

Other (OTH) AF: 0.656 AC: 1385 AN: 2112

Alfa AF: 0.643 Hom.: 3940

Bravo AF: 0.646

Asia WGS AF: 0.634 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.60
PhyloP100		-0.35

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: rs1017412; hg19: chr15-88412143;