chr15-87876193-T-G

Variant names:

• chr15-87876193-T-G
• rs7176429
• NM_001012338.3:c.*742A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001012338.3(NTRK3):​c.*742A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 233,082 control chromosomes in the GnomAD database, including 49,248 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 0.64 (31626 hom., cov: 32)
  • Exomes 𝑓: 0.66 (17622 hom.)
• Consequence: NTRK3 NM_001012338.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.81

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK3	NM_001012338.3	c.*742A>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000629765.3	NP_001012338.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK3	ENST00000629765	c.*742A>C		3_prime_UTR_variant	Exon 20 of 20	1	NM_001012338.3	ENSP00000485864.1
NTRK3	ENST00000394480	c.*742A>C		3_prime_UTR_variant	Exon 19 of 19	5		ENSP00000377990.1

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97529 AN: 151920 Hom.: 31594 Cov.: 32

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.561

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.690

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.680

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.657 AC: 53286 AN: 81044 Hom.: 17622 Cov.: 0 AF XY: 0.660 AC XY: 24631 AN XY: 37318

Gnomad4 AFR exome AF: 0.638

Gnomad4 AMR exome AF: 0.524

Gnomad4 ASJ exome AF: 0.680

Gnomad4 EAS exome AF: 0.633

Gnomad4 SAS exome AF: 0.481

Gnomad4 FIN exome AF: 0.659

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.656

GnomAD4 genome AF: 0.642 AC: 97611 AN: 152038 Hom.: 31626 Cov.: 32 AF XY: 0.638 AC XY: 47399 AN XY: 74326

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.561

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.598

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.690

Gnomad4 NFE AF: 0.680

Gnomad4 OTH AF: 0.634

Alfa AF: 0.661 Hom.: 65248

Bravo AF: 0.634

Asia WGS AF: 0.555 AC: 1932 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.017
DANN	Benign	0.40

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

Publications

LitVar

Other links and lift over

dbSNP: rs7176429; hg19: chr15-88419424;