1-154598557-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP2PP3

The NM_001111.5(ADAR):​c.1630C>G​(p.Arg544Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R544Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

ADAR
NM_001111.5 missense

Scores

6
11
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.29
Variant links:
Genes affected
ADAR (HGNC:225): (adenosine deaminase RNA specific) This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through conversion of adenosine to inosine. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the ADAR gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 16 curated pathogenic missense variants (we use a threshold of 10). The gene has 30 curated benign missense variants. Gene score misZ: 2.2714 (below the threshold of 3.09). Trascript score misZ: 3.4067 (above the threshold of 3.09). GenCC associations: The gene is linked to dyschromatosis symmetrica hereditaria, Aicardi-Goutieres syndrome, Aicardi-Goutieres syndrome 6, Leigh syndrome, familial infantile bilateral striatal necrosis.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADARNM_001111.5 linkc.1630C>G p.Arg544Gly missense_variant Exon 3 of 15 ENST00000368474.9 NP_001102.3 P55265-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADARENST00000368474.9 linkc.1630C>G p.Arg544Gly missense_variant Exon 3 of 15 1 NM_001111.5 ENSP00000357459.4 P55265-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461892
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Pathogenic
0.14
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.77
D;.;D;.;.;.;.;.;.;.;.
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.68
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.97
.;.;D;.;.;.;.;.;D;D;D
M_CAP
Uncertain
0.22
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.21
D
MutationAssessor
Benign
1.8
L;.;L;.;.;.;.;.;.;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Uncertain
-2.5
D;.;.;.;D;.;.;.;.;.;.
REVEL
Uncertain
0.64
Sift
Uncertain
0.0080
D;.;.;.;D;.;.;.;.;.;.
Sift4G
Uncertain
0.012
D;.;.;.;D;.;.;.;.;.;.
Polyphen
1.0
D;.;D;.;.;.;.;.;.;D;.
Vest4
0.83
MutPred
0.69
Loss of sheet (P = 0.0817);.;Loss of sheet (P = 0.0817);.;.;.;.;.;.;Loss of sheet (P = 0.0817);.;
MVP
0.83
MPC
1.0
ClinPred
0.96
D
GERP RS
5.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.45
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-154571033; API