chr16-66924885-C-A
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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.295G>T(p.Ala99Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,585,972 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00042 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
RRAD
NM_004165.3 missense
NM_004165.3 missense
Scores
5
14
Clinical Significance
Conservation
PhyloP100: 7.45
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=0.06434655).
BS2
?
High AC in GnomAd4 at 64 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRAD | NM_004165.3 | c.295G>T | p.Ala99Ser | missense_variant | 2/5 | ENST00000299759.11 | |
RRAD | NM_001128850.2 | c.295G>T | p.Ala99Ser | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRAD | ENST00000299759.11 | c.295G>T | p.Ala99Ser | missense_variant | 2/5 | 1 | NM_004165.3 | P1 | |
RRAD | ENST00000566577.1 | c.70G>T | p.Ala24Ser | missense_variant | 1/4 | 5 | |||
RRAD | ENST00000568915.5 | c.91G>T | p.Ala31Ser | missense_variant | 1/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000421 AC: 64AN: 151992Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000666 AC: 15AN: 225368Hom.: 0 AF XY: 0.0000160 AC XY: 2AN XY: 124658
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GnomAD4 exome AF: 0.0000342 AC: 49AN: 1433980Hom.: 0 Cov.: 30 AF XY: 0.0000322 AC XY: 23AN XY: 714226
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GnomAD4 genome ? AF: 0.000421 AC: 64AN: 151992Hom.: 0 Cov.: 32 AF XY: 0.000310 AC XY: 23AN XY: 74244
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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 | Aug 02, 2021 | The c.295G>T (p.A99S) alteration is located in exon 2 (coding exon 1) of the RRAD gene. This alteration results from a G to T substitution at nucleotide position 295, causing the alanine (A) at amino acid position 99 to be replaced by a serine (S). 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
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
1.1
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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