16-66922302-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_004165.3(RRAD):c.701C>T(p.Ala234Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000435 in 1,609,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
RRAD
NM_004165.3 missense
NM_004165.3 missense
Scores
12
5
2
Clinical Significance
Conservation
PhyloP100: 9.60
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 Uncertain_significance. Variant got 0 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.981
BS2
?
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RRAD | NM_004165.3 | c.701C>T | p.Ala234Val | missense_variant | 5/5 | ENST00000299759.11 | |
RRAD | NM_001128850.2 | c.701C>T | p.Ala234Val | missense_variant | 5/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RRAD | ENST00000299759.11 | c.701C>T | p.Ala234Val | missense_variant | 5/5 | 1 | NM_004165.3 | P1 | |
RRAD | ENST00000566577.1 | c.326-312C>T | intron_variant | 5 | |||||
RRAD | ENST00000568915.5 | c.240-383C>T | intron_variant | 5 | |||||
RRAD | ENST00000567791.1 | n.435C>T | non_coding_transcript_exon_variant | 2/3 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250544Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135502
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GnomAD4 exome AF: 0.00000412 AC: 6AN: 1457184Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724026
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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 | May 02, 2023 | The c.701C>T (p.A234V) 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 701, causing the alanine (A) at amino acid position 234 to be replaced by a valine (V). 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
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Pathogenic
D;D
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;.
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Pathogenic
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of MoRF binding (P = 0.3481);Gain of MoRF binding (P = 0.3481);
MVP
MPC
1.6
ClinPred
D
GERP RS
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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