6-73425426-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_138441.3(CGAS):c.1370G>A(p.Arg457His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. R457C) has been classified as Uncertain significance.
Frequency
Consequence
NM_138441.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CGAS | ENST00000370315.4 | c.1370G>A | p.Arg457His | missense_variant | Exon 5 of 5 | 1 | NM_138441.3 | ENSP00000359339.3 | ||
CGAS | ENST00000370318.5 | c.1332+38G>A | intron_variant | Intron 5 of 5 | 1 | ENSP00000359342.1 | ||||
CGAS | ENST00000680833.1 | c.1332+38G>A | intron_variant | Intron 5 of 5 | ENSP00000506638.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461762Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727178
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.1370G>A (p.R457H) alteration is located in exon 5 (coding exon 5) of the MB21D1 gene. This alteration results from a G to A substitution at nucleotide position 1370, causing the arginine (R) at amino acid position 457 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at