1-151721559-T-C

Variant names:

• chr1-151721559-T-C
• rs1673735361
• NM_001144956.3:c.23T>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.23T>C​(p.Leu8Pro) 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 1,178,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L8Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: RIIAD1 NM_001144956.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• 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=0.057492137).

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.23T>C	p.Leu8Pro	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.23T>C	p.Leu8Pro	missense	Exon 1 of 5	ENSP00000419249.1	A6NNX1
	RIIAD1	ENST00000326413.7	TSL:2	c.115-527T>C		intron	N/A	ENSP00000420280.1	C9JPK7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000170 AC: 2 AN: 1178232 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 569184

African (AFR) AF: 0.00 AC: 0 AN: 23504

American (AMR) AF: 0.00 AC: 0 AN: 10978

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17160

East Asian (EAS) AF: 0.00 AC: 0 AN: 26966

South Asian (SAS) AF: 0.00 AC: 0 AN: 49522

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3224

European-Non Finnish (NFE) AF: 0.00000206 AC: 2 AN: 970640

Other (OTH) AF: 0.00 AC: 0 AN: 47602

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.1
DANN	Benign	0.75
DEOGEN2	Benign	0.022	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.039	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
PhyloP100		-2.3
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.0060
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.016	D
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.19		Gain of disorder (P = 0.0504)
MVP		0.048
ClinPred		0.059	T
GERP RS		-0.96
PromoterAI		0.013	Neutral
Varity_R		0.13
gMVP		0.26
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs1673735361; hg19: chr1-151694035;