rs1554363589
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016616.5(NME8):āc.749A>Gā(p.Glu250Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E250K) has been classified as Uncertain significance.
Frequency
Consequence
NM_016616.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NME8 | NM_016616.5 | c.749A>G | p.Glu250Gly | missense_variant | 11/18 | ENST00000199447.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NME8 | ENST00000199447.9 | c.749A>G | p.Glu250Gly | missense_variant | 11/18 | 1 | NM_016616.5 | P1 | |
NME8 | ENST00000440017.5 | c.749A>G | p.Glu250Gly | missense_variant | 10/16 | 1 | P1 | ||
NME8 | ENST00000426106.1 | c.105+10484A>G | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461606Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727116
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2017 | This variant has not been reported in the literature in individuals with NME8-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with glycine at codon 250 of the NME8 protein (p.Glu250Gly). The glutamic acid residue is weakly conserved and there is a moderate physicochemical difference between glutamic acid and glycine. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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