9-32457172-C-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_014314.4(RIGI):c.2728G>T(p.Asp910Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. D910E) has been classified as Uncertain significance.
Frequency
Consequence
NM_014314.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIGI | NM_014314.4 | c.2728G>T | p.Asp910Tyr | missense_variant | 18/18 | ENST00000379883.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIGI | ENST00000379883.3 | c.2728G>T | p.Asp910Tyr | missense_variant | 18/18 | 1 | NM_014314.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251312Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135834
GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461720Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 727164
GnomAD4 genome ? AF: 0.000112 AC: 17AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.000107 AC XY: 8AN XY: 74430
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.2728G>T (p.D910Y) alteration is located in exon 18 (coding exon 18) of the DDX58 gene. This alteration results from a G to T substitution at nucleotide position 2728, causing the aspartic acid (D) at amino acid position 910 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 1039146). This variant has not been reported in the literature in individuals affected with DDX58-related conditions. This variant is present in population databases (rs377348789, gnomAD 0.03%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 910 of the DDX58 protein (p.Asp910Tyr). - |
Singleton-Merten syndrome 2 Other:1
not provided, no classification provided | phenotyping only | GenomeConnect - Invitae Patient Insights Network | - | Variant interpreted as Uncertain significance and reported on 10-30-2020 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at