1-156873647-C-G

Variant names:

• chr1-156873647-C-G
• NM_002529.4:c.865C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002529.4(NTRK1):​c.865C>G​(p.Gln289Glu) 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. 15/21 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. Q289H) 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: -0.504

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06857085).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NTRK1	NM_002529.4	c.865C>G	p.Gln289Glu	missense_variant	Exon 8 of 17	ENST00000524377.7	NP_002520.2
NTRK1	NM_001012331.2	c.865C>G	p.Gln289Glu	missense_variant	Exon 8 of 16		NP_001012331.1
NTRK1	NM_001007792.1	c.775C>G	p.Gln259Glu	missense_variant	Exon 9 of 17		NP_001007793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NTRK1	ENST00000524377.7	c.865C>G	p.Gln289Glu	missense_variant	Exon 8 of 17	1	NM_002529.4	ENSP00000431418.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	2.1
DANN	Benign	0.85
DEOGEN2	Benign	0.35	.;.;T;T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.089	N
LIST_S2	Benign	0.59	T;T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.069	T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;N;N;.
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-0.24	N;N;N;N
REVEL	Benign	0.078
Sift	Benign	0.35	T;T;T;T
Sift4G	Benign	0.38	T;T;T;T
Polyphen		0.012, 0.0	.;B;B;.
Vest4		0.15
MutPred		0.54		.;Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.67
MPC		0.26
ClinPred		0.065	T
GERP RS		3.0
Varity_R		0.14
gMVP		0.64

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: chr1-156843439;