1-156868145-G-C

Position:

• chr1-156868145-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002529.4(NTRK1):​c.470G>C​(p.Arg157Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. R157H) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NTRK1 NM_002529.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36856562).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK1	NM_002529.4	c.470G>C	p.Arg157Pro	missense_variant	5/17	ENST00000524377.7	NP_002520.2
NTRK1	NM_001012331.2	c.470G>C	p.Arg157Pro	missense_variant	5/16		NP_001012331.1
NTRK1	NM_001007792.1	c.380G>C	p.Arg127Pro	missense_variant	6/17		NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000524377.7	c.470G>C	p.Arg157Pro	missense_variant	5/17	1	NM_002529.4	ENSP00000431418.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.61	.;.;D;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.15	N
LIST_S2	Uncertain	0.87	D;D;D;D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.37	T;T;T;T
MetaSVM	Benign	-0.49	T
MutationAssessor	Uncertain	2.1	.;M;M;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.1	N;N;N;N
REVEL	Uncertain	0.56
Sift	Benign	0.057	T;T;T;T
Sift4G	Benign	0.20	T;T;T;T
Polyphen		0.94, 0.80	.;P;P;.
Vest4		0.47
MutPred		0.53		.;Gain of catalytic residue at W158 (P = 0.024);Gain of catalytic residue at W158 (P = 0.024);Gain of catalytic residue at W158 (P = 0.024);
MVP		0.85
MPC		0.43
ClinPred		0.83	D
GERP RS		-7.4
Varity_R		0.86
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156837937;