Genetic Variant TMIGD3:c.108-13173G>A (chr1-111503935-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001081976.3(TMIGD3):c.108-13173G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 984,732 control chromosomes in the GnomAD database, including 273,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.72 ( 39466 hom., cov: 33)

Exomes 𝑓: 0.75 ( 234216 hom. )

Consequence

TMIGD3
NM_001081976.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.223

Publications

18 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 1-111503935-C-T is Benign according to our data. Variant chr1-111503935-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243184.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001081976.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIGD3	NM_001081976.3		c.108-13173G>A		intron	N/A	NP_001075445.1
	TMIGD3	NM_001302680.2		c.108-15068G>A		intron	N/A	NP_001289609.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TMIGD3	ENST00000369717.8	TSL:1	c.108-13173G>A		intron	N/A	ENSP00000358731.4
	TMIGD3	ENST00000443498.5	TSL:3	c.90-15068G>A		intron	N/A	ENSP00000398770.1

Frequencies

GnomAD3 genomes

AF:

0.720

AC:

109091

AN:

151586

Hom.:

39421

Cov.:

show subpopulations

Gnomad AFR

AF:

0.642

Gnomad AMI

AF:

0.628

Gnomad AMR

AF:

0.787

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.687

Gnomad SAS

AF:

0.700

Gnomad FIN

AF:

0.746

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.746

Gnomad OTH

AF:

0.752

GnomAD4 exome

AF:

0.749

AC:

624281

AN:

833028

Hom.:

234216

Cov.:

AF XY:

0.750

AC XY:

288409

AN XY:

384680

show subpopulations

African (AFR)

AF:

0.637

AC:

10049

AN:

15780

American (AMR)

AF:

0.816

AC:

803

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

4232

AN:

5152

East Asian (EAS)

AF:

0.695

AC:

2524

AN:

3630

South Asian (SAS)

AF:

0.696

AC:

11452

AN:

16460

European-Finnish (FIN)

AF:

0.728

AC:

201

AN:

276

Middle Eastern (MID)

AF:

0.801

AC:

1298

AN:

1620

European-Non Finnish (NFE)

AF:

0.753

AC:

573379

AN:

761830

Other (OTH)

AF:

0.745

AC:

20343

AN:

27296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

8647

17294

25941

34588

43235

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19024

38048

57072

76096

95120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.720

AC:

109189

AN:

151704

Hom.:

39466

Cov.:

AF XY:

0.720

AC XY:

53374

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.642

AC:

26537

AN:

41308

American (AMR)

AF:

0.787

AC:

12009

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.820

AC:

2846

AN:

3470

East Asian (EAS)

AF:

0.687

AC:

3533

AN:

5144

South Asian (SAS)

AF:

0.701

AC:

3384

AN:

4826

European-Finnish (FIN)

AF:

0.746

AC:

7854

AN:

10522

Middle Eastern (MID)

AF:

0.830

AC:

239

AN:

288

European-Non Finnish (NFE)

AF:

0.746

AC:

50630

AN:

67872

Other (OTH)

AF:

0.754

AC:

1588

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1600

3200

4799

6399

7999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

840

1680

2520

3360

4200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.741

Hom.:

78783

Bravo

AF:

0.724

Asia WGS

AF:

0.713

AC:

2483

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.4

(source)

DANN

Benign

0.44

PhyloP100

0.22

PromoterAI

0.19

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over