1-151722126-A-T

Position:

• chr1-151722126-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIIAD1	NM_001144956.3	c.125A>T	p.His42Leu	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.125A>T	p.His42Leu	missense_variant	2/5	2	NM_001144956.3	ENSP00000419249.1
RIIAD1	ENST00000326413.7	c.155A>T	p.His52Leu	missense_variant	6/9	2		ENSP00000420280.1
RIIAD1	ENST00000451484.6	n.142A>T		non_coding_transcript_exon_variant	2/5	2
RIIAD1	ENST00000426175.5	n.-3A>T		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

May 29, 2024

The c.125A>T (p.H42L) alteration is located in exon 2 (coding exon 2) of the RIIAD1 gene. This alteration results from a A to T substitution at nucleotide position 125, causing the histidine (H) at amino acid position 42 to be replaced by a leucine (L). 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	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;T
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Benign	-0.37	T
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-10	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0020	D;D
Sift4G	Pathogenic	0.0	D;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

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: chr1-151694602;