16-66922086-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_004165.3(RRAD):c.917C>T(p.Ser306Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,606,152 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000030 ( 0 hom. )
Consequence
RRAD
NM_004165.3 missense
NM_004165.3 missense
Scores
7
6
6
Clinical Significance
Conservation
PhyloP100: 9.59
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 Likely_benign. Variant got -5 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.26815382).
BS2
?
High AC in GnomAdExome4 at 44 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRAD | NM_004165.3 | c.917C>T | p.Ser306Leu | missense_variant | 5/5 | ENST00000299759.11 | |
RRAD | NM_001128850.2 | c.917C>T | p.Ser306Leu | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRAD | ENST00000299759.11 | c.917C>T | p.Ser306Leu | missense_variant | 5/5 | 1 | NM_004165.3 | P1 | |
RRAD | ENST00000566577.1 | c.326-96C>T | intron_variant | 5 | |||||
RRAD | ENST00000568915.5 | c.240-167C>T | intron_variant | 5 | |||||
RRAD | ENST00000567791.1 | n.533+118C>T | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152248Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000558 AC: 14AN: 250898Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135722
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GnomAD4 exome AF: 0.0000303 AC: 44AN: 1453786Hom.: 0 Cov.: 31 AF XY: 0.0000416 AC XY: 30AN XY: 721224
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152366Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74502
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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 | Feb 07, 2023 | The c.917C>T (p.S306L) alteration is located in exon 5 (coding exon 4) of the RRAD gene. This alteration results from a C to T substitution at nucleotide position 917, causing the serine (S) at amino acid position 306 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.
M_CAP
Uncertain
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of sheet (P = 0.0221);Gain of sheet (P = 0.0221);
MVP
MPC
1.3
ClinPred
D
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