1-151721586-G-C

Position:

• chr1-151721586-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001144956.3(RIIAD1):​c.50G>C​(p.Ser17Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,160,610 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: RIIAD1 NM_001144956.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.00

Genes affected

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

ACMG classification

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=0.114893645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIIAD1	NM_001144956.3	c.50G>C	p.Ser17Thr	missense_variant	1/5	ENST00000479191.2	NP_001138428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIIAD1	ENST00000479191.2	c.50G>C	p.Ser17Thr	missense_variant	1/5	2	NM_001144956.3	ENSP00000419249.1
RIIAD1	ENST00000326413.7	c.115-500G>C		intron_variant		2		ENSP00000420280.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000138 AC: 16 AN: 1160610 Hom.: 0 Cov.: 30 AF XY: 0.0000125 AC XY: 7 AN XY: 559100

Gnomad4 AFR exome AF: 0.0000427

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000156

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Feb 27, 2023

The c.50G>C (p.S17T) alteration is located in exon 1 (coding exon 1) of the RIIAD1 gene. This alteration results from a G to C substitution at nucleotide position 50, causing the serine (S) at amino acid position 17 to be replaced by a threonine (T). 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	0.089
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	18
DANN	Benign	0.72
DEOGEN2	Benign	0.0090	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.060
Sift	Benign	0.24	T
Sift4G	Benign	0.12	T
Polyphen		0.73	P
Vest4		0.22
MutPred		0.13		Loss of disorder (P = 0.0969);
MVP		0.014
ClinPred		0.29	T
GERP RS		1.6
Varity_R		0.056
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs1432875071; hg19: chr1-151694062;