1-151721552-G-C

Variant names:

• chr1-151721552-G-C
• NM_001144956.3:c.16G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001144956.3(RIIAD1):​c.16G>C​(p.Gly6Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000017 in 1,179,562 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 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: 0.0000017 (0 hom.)
• Consequence: RIIAD1 NM_001144956.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.74
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.066141725).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001144956.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIIAD1	NM_001144956.3	MANE Select	c.16G>C	p.Gly6Arg	missense	Exon 1 of 5	NP_001138428.1	A6NNX1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIIAD1	ENST00000479191.2	TSL:2 MANE Select	c.16G>C	p.Gly6Arg	missense	Exon 1 of 5	ENSP00000419249.1	A6NNX1
	RIIAD1	ENST00000326413.7	TSL:2	c.115-534G>C		intron	N/A	ENSP00000420280.1	C9JPK7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000170 AC: 2 AN: 1179562 Hom.: 0 Cov.: 30 AF XY: 0.00000351 AC XY: 2 AN XY: 569904

African (AFR) AF: 0.00 AC: 0 AN: 23532

American (AMR) AF: 0.00 AC: 0 AN: 11050

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17100

East Asian (EAS) AF: 0.00 AC: 0 AN: 26986

South Asian (SAS) AF: 0.00 AC: 0 AN: 49722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3236

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 971690

Other (OTH) AF: 0.00 AC: 0 AN: 47656

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.6
DANN	Benign	0.70
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.1	T
PhyloP100		-2.7
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.025
Sift	Benign	0.072	T
Sift4G	Benign	0.52	T
Polyphen		0.23	B
Vest4		0.033
MutPred		0.15		Gain of phosphorylation at T3 (P = 0.0842)
MVP		0.030
ClinPred		0.13	T
GERP RS		-4.3
PromoterAI		0.19	Neutral
Varity_R		0.079
gMVP		0.077
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-151694028;