Variant 1-111483740-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020683.7(TMIGD3):c.991C>G(p.Pro331Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

TMIGD3
NM_020683.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0800

Variant links:

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]

TMIGD3 links:

TMIGD3 (HGNC:):

TMIGD3 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.066589564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMIGD3	NM_020683.7 linkuse as main transcript	c.991C>G	p.Pro331Ala	missense_variant	6/6	ENST00000369716.9	NP_065734.5	P0DMS9-2
TMIGD3	NM_001081976.3 linkuse as main transcript	c.748C>G	p.Pro250Ala	missense_variant	6/6		NP_001075445.1	P0DMS9-1
TMIGD3	NM_001302680.2 linkuse as main transcript	c.484C>G	p.Pro162Ala	missense_variant	5/5		NP_001289609.1	P0DMS9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMIGD3	ENST00000369716.9 linkuse as main transcript	c.991C>G	p.Pro331Ala	missense_variant	6/6	1	NM_020683.7	ENSP00000358730.4	P0DMS9-2
TMIGD3	ENST00000369717.8 linkuse as main transcript	c.748C>G	p.Pro250Ala	missense_variant	6/6	1		ENSP00000358731.4	P0DMS9-1
TMIGD3	ENST00000442484.2 linkuse as main transcript	n.570C>G		non_coding_transcript_exon_variant	5/5	1
TMIGD3	ENST00000443498.5 linkuse as main transcript	c.466C>G	p.Pro156Ala	missense_variant	5/5	3		ENSP00000398770.1	Q5QNY8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251360

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461672

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727146

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Aug 12, 2021

The c.991C>G (p.P331A) alteration is located in exon 6 (coding exon 6) of the ADORA3 gene. This alteration results from a C to G substitution at nucleotide position 991, causing the proline (P) at amino acid position 331 to be replaced by an alanine (A). 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

0.075

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.46

CADD

Benign

1.5

DANN

Benign

0.30

DEOGEN2

Benign

0.024

.;T;.

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.50

T;T;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.067

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.21

N;N;N

REVEL

Benign

0.049

Sift

Benign

0.091

T;T;T

Sift4G

Uncertain

0.042

D;T;T

Vest4

0.098

MutPred

0.48

Gain of helix (P = 0.0022);.;.;

MVP

0.23

MPC

0.038

ClinPred

0.072

GERP RS

-0.73

Varity_R

0.040

gMVP

0.079

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over