rs186068152
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016616.5(NME8):c.1601G>A(p.Arg534Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000991 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign 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. R534G) has been classified as Uncertain significance.
Frequency
Consequence
NM_016616.5 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 |
---|---|---|---|---|---|---|---|
NME8 | NM_016616.5 | c.1601G>A | p.Arg534Gln | missense_variant | 17/18 | ENST00000199447.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NME8 | ENST00000199447.9 | c.1601G>A | p.Arg534Gln | missense_variant | 17/18 | 1 | NM_016616.5 | P1 | |
NME8 | ENST00000440017.5 | c.1601G>A | p.Arg534Gln | missense_variant | 16/16 | 1 | P1 | ||
NME8 | ENST00000476435.1 | n.110G>A | non_coding_transcript_exon_variant | 1/2 | 1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251186Hom.: 0 AF XY: 0.0000516 AC XY: 7AN XY: 135742
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461648Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727122
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152202Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74396
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 24, 2018 | This sequence change replaces arginine with glutamine at codon 534 of the NME8 protein (p.Arg534Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs186068152, ExAC 0.02%). This variant has not been reported in the literature in individuals with NME8-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at