chr16-66924855-G-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004165.3(RRAD):ā€‹c.325C>Gā€‹(p.Arg109Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000418 in 1,435,390 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 (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000042 ( 0 hom. )

Consequence

RRAD
NM_004165.3 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.17
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 -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.31252345).
BS2
High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RRADNM_004165.3 linkuse as main transcriptc.325C>G p.Arg109Gly missense_variant 2/5 ENST00000299759.11
RRADNM_001128850.2 linkuse as main transcriptc.325C>G p.Arg109Gly missense_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RRADENST00000299759.11 linkuse as main transcriptc.325C>G p.Arg109Gly missense_variant 2/51 NM_004165.3 P1
RRADENST00000566577.1 linkuse as main transcriptc.100C>G p.Arg34Gly missense_variant 1/45
RRADENST00000568915.5 linkuse as main transcriptc.121C>G p.Arg41Gly missense_variant 1/35

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000174
AC:
4
AN:
229518
Hom.:
0
AF XY:
0.00000789
AC XY:
1
AN XY:
126714
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000234
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000418
AC:
6
AN:
1435390
Hom.:
0
Cov.:
30
AF XY:
0.00000280
AC XY:
2
AN XY:
715008
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000153
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.0000113
ExAC
AF:
0.0000165
AC:
2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.19
CADD
Uncertain
24
DANN
Benign
0.90
DEOGEN2
Benign
0.29
T;T
Eigen
Benign
0.069
Eigen_PC
Benign
0.15
FATHMM_MKL
Uncertain
0.91
D
LIST_S2
Benign
0.80
T;.
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
0.22
N;N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
0.010
N;N
REVEL
Uncertain
0.52
Sift
Benign
0.61
T;T
Sift4G
Benign
0.58
T;T
Polyphen
0.65
P;P
Vest4
0.51
MutPred
0.51
Loss of stability (P = 0.0098);Loss of stability (P = 0.0098);
MVP
0.85
MPC
1.4
ClinPred
0.35
T
GERP RS
4.1
Varity_R
0.51
gMVP
0.82

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs751752299; hg19: chr16-66958758; API