1-156876100-C-G

Position:

• chr1-156876100-C-G

Variant summary

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

The NM_002529.4(NTRK1):​c.1522C>G​(p.Arg508Gly) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NTRK1 NM_002529.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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=0.3350967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NTRK1	NM_002529.4	c.1522C>G	p.Arg508Gly	missense_variant	13/17	ENST00000524377.7	NP_002520.2
NTRK1	NM_001012331.2	c.1504C>G	p.Arg502Gly	missense_variant	12/16		NP_001012331.1
NTRK1	NM_001007792.1	c.1414C>G	p.Arg472Gly	missense_variant	13/17		NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000524377.7	c.1522C>G	p.Arg508Gly	missense_variant	13/17	1	NM_002529.4	ENSP00000431418	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Uncertain	0.075	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.84	.;.;D;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.36	N
LIST_S2	Uncertain	0.91	D;D;D;D
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.34	T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.0	.;.;M;.
MutationTaster	Benign	0.76	D;D;D;D
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.7	D;D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0070	D;D;D;D
Sift4G	Benign	0.089	T;T;T;T
Polyphen		0.0060, 0.20	.;B;B;.
Vest4		0.45
MutPred		0.45		.;.;Loss of stability (P = 0.0115);.;
MVP		0.86
MPC		0.53
ClinPred		0.78	D
GERP RS		1.9
Varity_R		0.64
gMVP		0.60

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: chr1-156845892;