rs780284256
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004304.5(ALK):c.2900C>A(p.Thr967Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000039 in 1,461,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T967T) has been classified as Likely benign.
Frequency
Consequence
NM_004304.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.2900C>A | p.Thr967Asn | missense_variant | 17/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.3753C>A | non_coding_transcript_exon_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.2900C>A | p.Thr967Asn | missense_variant | 17/29 | 1 | NM_004304.5 | P1 | |
ALK | ENST00000618119.4 | c.1769C>A | p.Thr590Asn | missense_variant | 16/28 | 5 | |||
ALK | ENST00000431873.6 | c.68C>A | p.Thr23Asn | missense_variant, NMD_transcript_variant | 1/14 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251482Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135914
GnomAD4 exome AF: 0.0000390 AC: 57AN: 1461574Hom.: 0 Cov.: 31 AF XY: 0.0000371 AC XY: 27AN XY: 727122
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 967 of the ALK protein (p.Thr967Asn). This variant is present in population databases (rs780284256, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ALK-related conditions. ClinVar contains an entry for this variant (Variation ID: 538224). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 2022 | The p.T967N variant (also known as c.2900C>A), located in coding exon 17 of the ALK gene, results from a C to A substitution at nucleotide position 2900. The threonine at codon 967 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at