Genetic Variant NTRK1:p.Asn202Tyr (chr1-156868534-A-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_002529.4(NTRK1):c.604A>T(p.Asn202Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N202S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NTRK1
NM_002529.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.00

Publications

0 publications found

Variant links:

Genes affected

NTRK1 (HGNC:8031): (neurotrophic receptor tyrosine kinase 1) This gene encodes a member of the neurotrophic tyrosine kinase receptor (NTKR) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. The presence of this kinase leads to cell differentiation and may play a role in specifying sensory neuron subtypes. Mutations in this gene have been associated with congenital insensitivity to pain, anhidrosis, self-mutilating behavior, cognitive disability and cancer. Alternate transcriptional splice variants of this gene have been found, but only three have been characterized to date. [provided by RefSeq, Jul 2008]

NTRK1 Gene-Disease associations (from GenCC):

hereditary sensory and autonomic neuropathy type 4
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
familial medullary thyroid carcinoma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NTRK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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_002529.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NTRK1	NM_002529.4	MANE Select	c.604A>T	p.Asn202Tyr	missense	Exon 6 of 17	NP_002520.2
NTRK1	NM_001012331.2		c.604A>T	p.Asn202Tyr	missense	Exon 6 of 16	NP_001012331.1	P04629-2
NTRK1	NM_001007792.1		c.514A>T	p.Asn172Tyr	missense	Exon 7 of 17	NP_001007793.1	P04629-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NTRK1	ENST00000524377.7	TSL:1 MANE Select	c.604A>T	p.Asn202Tyr	missense	Exon 6 of 17	ENSP00000431418.1	P04629-1
NTRK1	ENST00000368196.7	TSL:1	c.604A>T	p.Asn202Tyr	missense	Exon 6 of 16	ENSP00000357179.3	P04629-2
NTRK1	ENST00000358660.3	TSL:2	c.604A>T	p.Asn202Tyr	missense	Exon 6 of 16	ENSP00000351486.3	J3KP20

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1406918

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694646

African (AFR)

AF:

0.00

AC:

AN:

32022

American (AMR)

AF:

0.00

AC:

AN:

36968

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25232

East Asian (EAS)

AF:

0.00

AC:

AN:

36412

South Asian (SAS)

AF:

0.00

AC:

AN:

79760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083190

Other (OTH)

AF:

0.00

AC:

AN:

58264

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.79

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.81

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.72

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

PhyloP100

4.0

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.18

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

0.76

Vest4

0.68

MutPred

0.51

Gain of phosphorylation at N202 (P = 0.0215)

MVP

0.85

MPC

0.85

ClinPred

1.0

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.71

gMVP

0.66

Mutation Taster

=68/32

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over