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GeneBe

16-66925016-G-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004165.3(RRAD):c.164C>A(p.Ala55Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000439 in 1,413,522 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

RRAD
NM_004165.3 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.06885153).
BS2
High AC in GnomAd at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RRADNM_004165.3 linkuse as main transcriptc.164C>A p.Ala55Asp missense_variant 2/5 ENST00000299759.11
RRADNM_001128850.2 linkuse as main transcriptc.164C>A p.Ala55Asp missense_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RRADENST00000299759.11 linkuse as main transcriptc.164C>A p.Ala55Asp missense_variant 2/51 NM_004165.3 P1
RRADENST00000568915.5 linkuse as main transcript upstream_gene_variant 5

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152058
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00124
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000500
AC:
4
AN:
80020
Hom.:
0
AF XY:
0.0000432
AC XY:
2
AN XY:
46276
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000140
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000591
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000432
GnomAD4 exome
AF:
0.0000325
AC:
41
AN:
1261464
Hom.:
0
Cov.:
30
AF XY:
0.0000307
AC XY:
19
AN XY:
619324
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000160
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000352
Gnomad4 SAS exome
AF:
0.0000319
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000218
Gnomad4 OTH exome
AF:
0.000233
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152058
Hom.:
0
Cov.:
33
AF XY:
0.000162
AC XY:
12
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00124
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.000227

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 submitterclinical testingAmbry GeneticsAug 17, 2022The c.164C>A (p.A55D) alteration is located in exon 2 (coding exon 1) of the RRAD gene. This alteration results from a C to A substitution at nucleotide position 164, causing the alanine (A) at amino acid position 55 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.51
Cadd
Benign
16
Dann
Benign
0.65
DEOGEN2
Benign
0.17
T;T
Eigen
Benign
-0.78
Eigen_PC
Benign
-0.69
FATHMM_MKL
Benign
0.23
N
LIST_S2
Benign
0.59
T;.
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.069
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.20
N;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.69
T
PROVEAN
Benign
-0.35
N;N
REVEL
Benign
0.083
Sift
Benign
0.62
T;T
Sift4G
Benign
0.61
T;T
Polyphen
0.0
B;B
Vest4
0.096
MutPred
0.17
Loss of helix (P = 0.0304);Loss of helix (P = 0.0304);
MVP
0.67
MPC
0.95
ClinPred
0.017
T
GERP RS
3.4
Varity_R
0.15
gMVP
0.49

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1010302141; hg19: chr16-66958919; API