rs150579345
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP6
The NM_002529.4(NTRK1):c.1741G>A(p.Glu581Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000123 in 1,613,644 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E581G) has been classified as Uncertain significance.
Frequency
Consequence
NM_002529.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NTRK1 | NM_002529.4 | c.1741G>A | p.Glu581Lys | missense_variant | 14/17 | ENST00000524377.7 | |
NTRK1 | NM_001012331.2 | c.1723G>A | p.Glu575Lys | missense_variant | 13/16 | ||
NTRK1 | NM_001007792.1 | c.1633G>A | p.Glu545Lys | missense_variant | 14/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NTRK1 | ENST00000524377.7 | c.1741G>A | p.Glu581Lys | missense_variant | 14/17 | 1 | NM_002529.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000140 AC: 35AN: 250330Hom.: 0 AF XY: 0.000140 AC XY: 19AN XY: 135636
GnomAD4 exome AF: 0.000123 AC: 180AN: 1461342Hom.: 0 Cov.: 34 AF XY: 0.000114 AC XY: 83AN XY: 726982
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152302Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74474
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2021 | The p.E575K variant (also known as c.1723G>A), located in coding exon 13 of the NTRK1 gene, results from a G to A substitution at nucleotide position 1723. The glutamic acid at codon 575 is replaced by lysine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Hereditary insensitivity to pain with anhidrosis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 22, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at