1-111490662-T-C

Position:

• chr1-111490662-T-C

Variant summary

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

The NM_020683.7(TMIGD3):​c.451A>G​(p.Ile151Val) variant causes a missense 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TMIGD3 NM_020683.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0730

Genes affected

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

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=0.07013193).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMIGD3	NM_020683.7	c.451A>G	p.Ile151Val	missense_variant	2/6	ENST00000369716.9	NP_065734.5
TMIGD3	NM_001081976.3	c.208A>G	p.Ile70Val	missense_variant	2/6		NP_001075445.1
TMIGD3	NM_001302680.2	c.108-1795A>G		intron_variant			NP_001289609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMIGD3	ENST00000369716.9	c.451A>G	p.Ile151Val	missense_variant	2/6	1	NM_020683.7	ENSP00000358730.4
TMIGD3	ENST00000369717.8	c.208A>G	p.Ile70Val	missense_variant	2/6	1		ENSP00000358731.4
TMIGD3	ENST00000443498.5	c.90-1795A>G		intron_variant		3		ENSP00000398770.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Oct 21, 2021

The c.451A>G (p.I151V) alteration is located in exon 2 (coding exon 2) of the ADORA3 gene. This alteration results from a A to G substitution at nucleotide position 451, causing the isoleucine (I) at amino acid position 151 to be replaced by a valine (V). 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	0.093
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	4.3
DANN	Benign	0.73
DEOGEN2	Benign	0.0056	.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.50	T;T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.070	T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.13	N;N
REVEL	Benign	0.014
Sift	Benign	0.11	T;T
Sift4G	Benign	0.40	T;T
Vest4		0.047
MutPred		0.66		Loss of loop (P = 0.0986);.;
MVP		0.040
MPC		0.029
ClinPred		0.52	D
GERP RS		-3.1
Varity_R		0.025
gMVP		0.14

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: chr1-112033284;