rs193920740
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_021008.4(DEAF1):c.1526G>A(p.Arg509Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000049 in 1,613,564 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. R509W) has been classified as Uncertain significance.
Frequency
Consequence
NM_021008.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DEAF1 | NM_021008.4 | c.1526G>A | p.Arg509Gln | missense_variant | 11/12 | ENST00000382409.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DEAF1 | ENST00000382409.4 | c.1526G>A | p.Arg509Gln | missense_variant | 11/12 | 1 | NM_021008.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152024Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250720Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135584
GnomAD4 exome AF: 0.0000499 AC: 73AN: 1461540Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 26AN XY: 727054
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152024Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3AN XY: 74238
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 25, 2023 | The c.1526G>A (p.R509Q) alteration is located in exon 11 (coding exon 11) of the DEAF1 gene. This alteration results from a G to A substitution at nucleotide position 1526, causing the arginine (R) at amino acid position 509 to be replaced by a glutamine (Q). 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 15, 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DEAF1 protein function. ClinVar contains an entry for this variant (Variation ID: 161743). This variant has not been reported in the literature in individuals affected with DEAF1-related conditions. This variant is present in population databases (rs193920740, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 509 of the DEAF1 protein (p.Arg509Gln). - |
Malignant tumor of prostate Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Science for Life laboratory, Karolinska Institutet | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at