1-111500010-A-T

Variant names:

• chr1-111500010-A-T
• rs2229155
• NM_000677.4:c.897T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000677.4(ADORA3):​c.897T>A​(p.Ala299Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADORA3 NM_000677.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10
• Publications: 27 publications found

Genes affected

ADORA3 (HGNC:268): (adenosine A3 receptor) This gene encodes a protein that belongs to the family of adenosine receptors, which are G-protein-coupled receptors that are involved in a variety of intracellular signaling pathways and physiological functions. The receptor encoded by this gene mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death. Alternative splicing results in multiple transcript variants. This gene shares its 5' terminal exon with some transcripts from overlapping GeneID:57413, which encodes an immunoglobulin domain-containing protein. [provided by RefSeq, Nov 2014]

TMIGD3 (HGNC:51375): (transmembrane and immunoglobulin domain containing 3) This gene encodes a transmembrane and immunoglobulin domain-containing protein. Alternative splicing results in multiple transcript variants, one of which shares its 5' terminal exon with that of the overlapping adenosine A3 receptor gene (GeneID:140), thus resulting in a fusion product. [provided by RefSeq, Nov 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP7: Synonymous conserved (PhyloP=2.1 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA3	NM_000677.4	MANE Select	c.897T>A	p.Ala299Ala	synonymous	Exon 2 of 2	NP_000668.1
	TMIGD3	NM_020683.7	MANE Select	c.350+2995T>A		intron	N/A	NP_065734.5
	ADORA3	NM_001302679.2		c.462T>A	p.Ala154Ala	synonymous	Exon 2 of 2	NP_001289608.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADORA3	ENST00000241356.5	TSL:1 MANE Select	c.897T>A	p.Ala299Ala	synonymous	Exon 2 of 2	ENSP00000241356.4
	TMIGD3	ENST00000369716.9	TSL:1 MANE Select	c.350+2995T>A		intron	N/A	ENSP00000358730.4
	TMIGD3	ENST00000369717.8	TSL:1	c.108-9248T>A		intron	N/A	ENSP00000358731.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461844 Hom.: 0 Cov.: 57 AF XY: 0.00 AC XY: 0 AN XY: 727226

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111978

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 227393

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.43
PhyloP100		2.1
Mutation Taster		=100/0	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

dbSNP: rs2229155; hg19: chr1-112042632;