rs779939725

Variant names:

• chr1-154602095-C-A
• rs779939725
• NM_001111.5:c.547G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-154602095-C-A
• chr1-154602095-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP2 PP3_Moderate

The NM_001111.5(ADAR):​c.547G>T​(p.Gly183Cys) 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 1,461,886 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. G183S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADAR NM_001111.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 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, 0.853

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAR	NM_001111.5	c.547G>T	p.Gly183Cys	missense_variant	Exon 2 of 15	ENST00000368474.9	NP_001102.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9	c.547G>T	p.Gly183Cys	missense_variant	Exon 2 of 15	1	NM_001111.5	ENSP00000357459.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251478 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135906

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461886 Hom.: 0 Cov.: 89 AF XY: 0.00000138 AC XY: 1 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.038	T
BayesDel_noAF	Uncertain	-0.010
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;D;.
Eigen	Uncertain	0.31
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Pathogenic	3.0	M;M;M
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.6	D;.;.
REVEL	Uncertain	0.48
Sift	Uncertain	0.0020	D;.;.
Sift4G	Uncertain	0.0070	D;.;.
Polyphen		1.0	D;D;D
Vest4		0.63
MutPred		0.66		Gain of methylation at K184 (P = 0.0151);Gain of methylation at K184 (P = 0.0151);Gain of methylation at K184 (P = 0.0151);
MVP		0.81
MPC		0.91
ClinPred		0.90	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.82
gMVP		0.36

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

LitVar

Other links and lift over

dbSNP: rs779939725; hg19: chr1-154574571;