NM_001144956.3:c.125A>T

Variant names:

• chr1-151722126-A-T
• NM_001144956.3:c.125A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001144956.3(RIIAD1):​c.125A>T​(p.His42Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIIAD1 NM_001144956.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.39
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.125A>T	p.His42Leu	missense	Exon 2 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.125A>T	p.His42Leu	missense	Exon 2 of 5	ENSP00000419249.1	A6NNX1
	RIIAD1	ENST00000326413.7	TSL:2	c.155A>T	p.His52Leu	missense	Exon 6 of 9	ENSP00000420280.1	C9JPK7
	RIIAD1	ENST00000451484.6	TSL:2	n.142A>T		non_coding_transcript_exon	Exon 2 of 5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Benign	23
DANN	Benign	0.97
DEOGEN2	Benign	0.34	T
Eigen	Uncertain	0.55
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.37	T
PhyloP100		2.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-10	D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.60
MutPred		0.49		Loss of catalytic residue at R40 (P = 0.0522)
MVP		0.20
ClinPred		0.99	D
GERP RS		4.8
Varity_R		0.53
gMVP		0.55
Mutation Taster		=80/20	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

hg19: chr1-151694602;