1-203165347-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_000674.3(ADORA1):​c.428T>C​(p.Met143Thr) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M143V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

ADORA1
NM_000674.3 missense

Scores

3
15
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.11
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.879

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ADORA1NM_000674.3 linkuse as main transcriptc.428T>C p.Met143Thr missense_variant 4/4 ENST00000337894.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ADORA1ENST00000337894.9 linkuse as main transcriptc.428T>C p.Met143Thr missense_variant 4/42 NM_000674.3 P1P30542-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 02, 2021The c.428T>C (p.M143T) alteration is located in exon 4 (coding exon 2) of the ADORA1 gene. This alteration results from a T to C substitution at nucleotide position 428, causing the methionine (M) at amino acid position 143 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
Pathogenic
0.60
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.70
D;D;D;.
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.36
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Uncertain
0.96
.;.;D;D
M_CAP
Uncertain
0.11
D
MetaRNN
Pathogenic
0.88
D;D;D;D
MetaSVM
Uncertain
-0.099
T
MutationAssessor
Uncertain
2.6
M;M;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Pathogenic
-4.5
D;D;D;.
REVEL
Uncertain
0.62
Sift
Uncertain
0.0010
D;D;D;.
Sift4G
Uncertain
0.0050
D;D;D;D
Polyphen
0.56
P;P;P;.
Vest4
0.63
MutPred
0.77
Gain of glycosylation at M143 (P = 0.0789);Gain of glycosylation at M143 (P = 0.0789);Gain of glycosylation at M143 (P = 0.0789);.;
MVP
0.85
MPC
1.1
ClinPred
0.96
D
GERP RS
5.0
Varity_R
0.85
gMVP
0.90

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: chr1-203134475; API