16-66922134-C-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004165.3(RRAD):c.869G>A(p.Ser290Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,613,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000022 ( 0 hom. )
Consequence
RRAD
NM_004165.3 missense
NM_004165.3 missense
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 5.86
Genes affected
RRAD (HGNC:10446): (RRAD, Ras related glycolysis inhibitor and calcium channel regulator) Predicted to enable GTP binding activity and calcium channel regulator activity. Predicted to be involved in small GTPase mediated signal transduction. Predicted to be located in cytosol. Predicted to be active in plasma membrane. Implicated in type 2 diabetes mellitus. Biomarker of congestive heart failure. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.01125586).
BS2
?
High AC in GnomAdExome4 at 32 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRAD | NM_004165.3 | c.869G>A | p.Ser290Asn | missense_variant | 5/5 | ENST00000299759.11 | |
RRAD | NM_001128850.2 | c.869G>A | p.Ser290Asn | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRAD | ENST00000299759.11 | c.869G>A | p.Ser290Asn | missense_variant | 5/5 | 1 | NM_004165.3 | P1 | |
RRAD | ENST00000566577.1 | c.326-144G>A | intron_variant | 5 | |||||
RRAD | ENST00000568915.5 | c.240-215G>A | intron_variant | 5 | |||||
RRAD | ENST00000567791.1 | n.533+70G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152234Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000135 AC: 34AN: 251270Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135874
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GnomAD4 exome AF: 0.0000219 AC: 32AN: 1460896Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 726508
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152352Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74504
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 06, 2023 | The c.869G>A (p.S290N) alteration is located in exon 5 (coding exon 4) of the RRAD gene. This alteration results from a G to A substitution at nucleotide position 869, causing the serine (S) at amino acid position 290 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;.
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of phosphorylation at S290 (P = 0.0067);Loss of phosphorylation at S290 (P = 0.0067);
MVP
MPC
0.59
ClinPred
T
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at