1-203165382-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000674.3(ADORA1):c.463G>A(p.Ala155Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,452,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: ADORA1 NM_000674.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.26

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12185794).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADORA1	NM_000674.3	c.463G>A	p.Ala155Thr	missense_variant	4/4	ENST00000337894.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADORA1	ENST00000337894.9	c.463G>A	p.Ala155Thr	missense_variant	4/4	2	NM_000674.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1452590 Hom.: 0 Cov.: 31 AF XY: 0.00000416 AC XY: 3 AN XY: 721636

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000451

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

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

Oct 10, 2023

The c.463G>A (p.A155T) alteration is located in exon 4 (coding exon 2) of the ADORA1 gene. This alteration results from a G to A substitution at nucleotide position 463, causing the alanine (A) at amino acid position 155 to be replaced by a threonine (T). 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	Benign	0.091
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Benign	0.97
DEOGEN2	Benign	0.14	T;T;T;.
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.67	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.23	N;N;N;.
MutationTaster	Benign	1.0	D;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.82	N;N;N;.
REVEL	Benign	0.11
Sift	Benign	0.59	T;T;T;.
Sift4G	Benign	0.61	T;T;T;T
Polyphen		0.0	B;B;B;.
Vest4		0.021
MutPred		0.56		Loss of catalytic residue at A155 (P = 0.0326);Loss of catalytic residue at A155 (P = 0.0326);Loss of catalytic residue at A155 (P = 0.0326);.;
MVP		0.78
MPC		0.69
ClinPred		0.15	T
GERP RS		4.1
Varity_R		0.14
gMVP		0.45

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: chr1-203134510;