2-29920157-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_004304.5(ALK):āc.503T>Cā(p.Phe168Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000088 in 1,613,604 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F168L) has been classified as Uncertain significance.
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.503T>C | p.Phe168Ser | missense_variant | 1/29 | ENST00000389048.8 | |
ALK | XR_001738688.3 | n.1430T>C | non_coding_transcript_exon_variant | 1/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.503T>C | p.Phe168Ser | missense_variant | 1/29 | 1 | NM_004304.5 | P1 | |
ENST00000669284.1 | n.157+35092T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249404Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135408
GnomAD4 exome AF: 0.0000937 AC: 137AN: 1461386Hom.: 0 Cov.: 31 AF XY: 0.0000798 AC XY: 58AN XY: 727002
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 24, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 168 of the ALK protein (p.Phe168Ser). This variant is present in population databases (rs755498584, gnomAD 0.004%). 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: 404315). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2024 | The p.F168S variant (also known as c.503T>C), located in coding exon 1 of the ALK gene, results from a T to C substitution at nucleotide position 503. The phenylalanine at codon 168 is replaced by serine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious 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