1-156874392-C-G

Position:

• chr1-156874392-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_002529.4(NTRK1):​c.1187C>G​(p.Ser396Trp) 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 pathogenic 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. S396L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NTRK1 NM_002529.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.01

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK1	NM_002529.4	c.1187C>G	p.Ser396Trp	missense_variant	9/17	ENST00000524377.7	NP_002520.2
NTRK1	NM_001012331.2	c.1178-179C>G		intron_variant			NP_001012331.1
NTRK1	NM_001007792.1	c.1088-179C>G		intron_variant			NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000524377.7	c.1187C>G	p.Ser396Trp	missense_variant	9/17	1	NM_002529.4	ENSP00000431418.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Uncertain	0.062	T
BayesDel_noAF	Benign	-0.15
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.70	D
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.24	D
MetaRNN	Pathogenic	0.75	D
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.37
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.022	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.36		Loss of disorder (P = 4e-04);
MVP		0.92
MPC		0.98
ClinPred		0.97	D
GERP RS		4.8
Varity_R		0.18
gMVP		0.56

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-156844184;