Variant 1-151721598-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001144956.3(RIIAD1):c.62T>C(p.Leu21Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000845 in 1,301,830 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000087 ( 0 hom. )

Consequence

RIIAD1
NM_001144956.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.837

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22324109).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIIAD1	NM_001144956.3 linkuse as main transcript	c.62T>C	p.Leu21Pro	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.62T>C	p.Leu21Pro	missense_variant	1/5	2	NM_001144956.3	ENSP00000419249.1		A6NNX1
RIIAD1	ENST00000326413.7 linkuse as main transcript	c.115-488T>C		intron_variant		2		ENSP00000420280.1		C9JPK7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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

GnomAD4 exome

AF:

0.00000870

AC:

AN:

1149728

Hom.:

Cov.:

AF XY:

0.00000543

AC XY:

AN XY:

552514

show subpopulations

Gnomad4 AFR exome

AF:

0.0000429

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000743

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000734

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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

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

Apr 19, 2024

The c.62T>C (p.L21P) alteration is located in exon 1 (coding exon 1) of the RIIAD1 gene. This alteration results from a T to C substitution at nucleotide position 62, causing the leucine (L) at amino acid position 21 to be replaced by a proline (P). 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

Pathogenic

0.58

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.021

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.29

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.62

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.58

REVEL

Benign

0.18

Sift

Benign

0.13

Sift4G

Uncertain

0.032

Polyphen

0.77

Vest4

0.44

MutPred

0.41

Gain of disorder (P = 0.0089);

MVP

0.17

ClinPred

0.96

GERP RS

2.1

Varity_R

0.17

gMVP

0.48

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