Variant 1-151721565-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001144956.3(RIIAD1):c.29G>T(p.Arg10Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000347 in 1,326,928 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 1 hom. )

Consequence

RIIAD1
NM_001144956.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.183

Variant links:

Genes affected

RIIAD1 (HGNC:26686): (regulatory subunit of type II PKA R-subunit domain containing 1)

RIIAD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0039756596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIIAD1	NM_001144956.3 linkuse as main transcript	c.29G>T	p.Arg10Leu	missense_variant	1/5	ENST00000479191.2	NP_001138428.1	A6NNX1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIIAD1	ENST00000479191.2 linkuse as main transcript	c.29G>T	p.Arg10Leu	missense_variant	1/5	2	NM_001144956.3	ENSP00000419249.1		A6NNX1
RIIAD1	ENST00000326413.7 linkuse as main transcript	c.115-521G>T		intron_variant		2		ENSP00000420280.1		C9JPK7

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000380

AC:

AN:

15802

Hom.:

AF XY:

0.000491

AC XY:

AN XY:

10192

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000940

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000365

AC:

429

AN:

1174682

Hom.:

Cov.:

AF XY:

0.000358

AC XY:

203

AN XY:

567212

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.0000371

Gnomad4 SAS exome

AF:

0.000102

Gnomad4 FIN exome

AF:

0.0000349

Gnomad4 NFE exome

AF:

0.000386

Gnomad4 OTH exome

AF:

0.000253

GnomAD4 genome

AF:

0.000210

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000945

Bravo

AF:

0.000155

ExAC

AF:

0.000440

AC:

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 17, 2024

The c.29G>T (p.R10L) alteration is located in exon 1 (coding exon 1) of the RIIAD1 gene. This alteration results from a G to T substitution at nucleotide position 29, causing the arginine (R) at amino acid position 10 to be replaced by a leucine (L). 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

0.063

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.2

DANN

Benign

0.74

DEOGEN2

Benign

0.012

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.050

LIST_S2

Benign

0.47

M_CAP

Benign

0.0087

MetaRNN

Benign

0.0040

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.85

REVEL

Benign

0.047

Sift

Benign

0.27

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.080

MVP

0.22

ClinPred

0.0099

GERP RS

-4.3

Varity_R

0.042

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over