rs774836034
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2
The NM_004304.5(ALK):c.3178C>T(p.Arg1060Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,416 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1060H) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALK | NM_004304.5 | c.3178C>T | p.Arg1060Cys | missense_variant | 20/29 | ENST00000389048.8 | |
ALK | NM_001353765.2 | c.-27C>T | 5_prime_UTR_variant | 1/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALK | ENST00000389048.8 | c.3178C>T | p.Arg1060Cys | missense_variant | 20/29 | 1 | NM_004304.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248588Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134596
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461268Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 726966
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74324
ClinVar
Submissions by phenotype
Neuroblastoma, susceptibility to, 3 Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 21, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 565659). This variant has not been reported in the literature in individuals affected with ALK-related conditions. This variant is present in population databases (rs774836034, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1060 of the ALK protein (p.Arg1060Cys). - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 21, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at