rs771646303

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139243.4(ADAD1):​c.274C>A​(p.Arg92Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,454,272 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R92C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADAD1
NM_139243.4 missense

Scores

7
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.47
Variant links:
Genes affected
ADAD1 (HGNC:30713): (adenosine deaminase domain containing 1) Predicted to enable double-stranded RNA adenosine deaminase activity; double-stranded RNA binding activity; and tRNA-specific adenosine deaminase activity. Predicted to be involved in RNA processing and adenosine to inosine editing. Predicted to act upstream of or within spermatid development. Predicted to be located in nucleus. Predicted to be active in cytoplasm and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18956).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAD1NM_139243.4 linkc.274C>A p.Arg92Ser missense_variant Exon 4 of 13 ENST00000296513.7 NP_640336.1 Q96M93-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAD1ENST00000296513.7 linkc.274C>A p.Arg92Ser missense_variant Exon 4 of 13 2 NM_139243.4 ENSP00000296513.2 Q96M93-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1454272
Hom.:
0
Cov.:
31
AF XY:
0.00000277
AC XY:
2
AN XY:
723238
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:
0.0000119
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-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
Uncertain
0.50
BayesDel_addAF
Benign
-0.077
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.030
T;T;T;.;.
Eigen
Uncertain
0.27
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.75
T;T;T;T;T
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.19
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
.;L;.;L;.
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-2.5
N;N;N;N;N
REVEL
Benign
0.18
Sift
Benign
0.077
T;D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D;D
Polyphen
0.98, 0.99
.;D;.;D;.
Vest4
0.39, 0.38, 0.38
MutPred
0.54
Loss of catalytic residue at R92 (P = 0.0026);Loss of catalytic residue at R92 (P = 0.0026);Loss of catalytic residue at R92 (P = 0.0026);Loss of catalytic residue at R92 (P = 0.0026);.;
MVP
0.15
MPC
0.26
ClinPred
0.95
D
GERP RS
5.2
Varity_R
0.17
gMVP
0.43

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: chr4-123302248; API