chr1-203165701-C-A

Position:

• chr1-203165701-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000674.3(ADORA1):​c.782C>A​(p.Pro261Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ADORA1 NM_000674.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01

Genes affected

ADORA1 (HGNC:262): (adenosine A1 receptor) The protein encoded by this gene is an adenosine receptor that belongs to the G-protein coupled receptor 1 family. There are 3 types of adenosine receptors, each with a specific pattern of ligand binding and tissue distribution, and together they regulate a diverse set of physiologic functions. The type A1 receptors inhibit adenylyl cyclase, and play a role in the fertilization process. Animal studies also suggest a role for A1 receptors in kidney function and ethanol intoxication. Transcript variants with alternative splicing in the 5' UTR have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.746

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADORA1	NM_000674.3	c.782C>A	p.Pro261Gln	missense_variant	4/4	ENST00000337894.9	NP_000665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADORA1	ENST00000337894.9	c.782C>A	p.Pro261Gln	missense_variant	4/4	2	NM_000674.3	ENSP00000338435.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D;D;D;.
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.88	.;.;D;D
M_CAP	Benign	0.024	T
MetaRNN	Pathogenic	0.75	D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.5	M;M;M;.
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.8	D;D;D;.
REVEL	Benign	0.17
Sift	Benign	0.062	T;T;T;.
Sift4G	Benign	0.096	T;T;T;D
Polyphen		0.95	P;P;P;.
Vest4		0.64
MutPred		0.19		Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);.;
MVP		0.89
MPC		1.6
ClinPred		0.99	D
GERP RS		5.5
Varity_R		0.50
gMVP		0.67

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

LitVar

Other links and lift over

dbSNP: rs17852405; hg19: chr1-203134829;