1-151722120-G-A

Position:

• chr1-151722120-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001144956.3(RIIAD1):​c.119G>A​(p.Arg40Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIIAD1 NM_001144956.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.08

Genes affected

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

RIIAD1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27534866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIIAD1	NM_001144956.3	c.119G>A	p.Arg40Lys	missense_variant	2/5	ENST00000479191.2	NP_001138428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIIAD1	ENST00000479191.2	c.119G>A	p.Arg40Lys	missense_variant	2/5	2	NM_001144956.3	ENSP00000419249.1
RIIAD1	ENST00000326413.7	c.149G>A	p.Arg50Lys	missense_variant	6/9	2		ENSP00000420280.1
RIIAD1	ENST00000451484.6	n.136G>A		non_coding_transcript_exon_variant	2/5	2
RIIAD1	ENST00000426175.5	n.-9G>A		upstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 14, 2024

The c.119G>A (p.R40K) alteration is located in exon 2 (coding exon 2) of the RIIAD1 gene. This alteration results from a G to A substitution at nucleotide position 119, causing the arginine (R) at amino acid position 40 to be replaced by a lysine (K). 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	0.26
BayesDel_addAF	Benign	-0.000069	T
BayesDel_noAF	Benign	-0.24
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.068	.;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.83	T;T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.95	T
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-2.5	D;N
REVEL	Benign	0.19
Sift	Benign	0.064	T;T
Sift4G	Pathogenic	0.0	D;D
Polyphen		0.99	.;D
Vest4		0.33
MutPred		0.47		.;Gain of ubiquitination at R40 (P = 0.0337);
MVP		0.048
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.23
gMVP		0.29

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-151694596;