1-111503918-A-G

Variant names:

• chr1-111503918-A-G
• rs1544224
• ENST00000369717.8:c.108-13156T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000369717.8(TMIGD3):​c.108-13156T>C 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 984,730 control chromosomes in the GnomAD database, including 273,787 homozygotes. 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: 𝑓 0.72 (39527 hom., cov: 33)
  • Exomes 𝑓: 0.75 (234260 hom.)
• Consequence: TMIGD3 ENST00000369717.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189
• Publications: 16 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMIGD3	NM_001081976.3	c.108-13156T>C		intron_variant	Intron 1 of 5		NP_001075445.1
TMIGD3	NM_001302680.2	c.108-15051T>C		intron_variant	Intron 1 of 4		NP_001289609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TMIGD3	ENST00000369717.8	c.108-13156T>C		intron_variant	Intron 1 of 5	1		ENSP00000358731.4
TMIGD3	ENST00000443498.5	c.90-15051T>C		intron_variant	Intron 1 of 4	3		ENSP00000398770.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109169 AN: 151582 Hom.: 39482 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.626

Gnomad AMR AF: 0.787

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.686

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: 624344 AN: 833030 Hom.: 234260 Cov.: 35 AF XY: 0.750 AC XY: 288436 AN XY: 384674

African (AFR) AF: 0.639 AC: 10086 AN: 15784

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: 11453 AN: 16458

European-Finnish (FIN) AF: 0.728 AC: 201 AN: 276

Middle Eastern (MID) AF: 0.802 AC: 1299 AN: 1620

European-Non Finnish (NFE) AF: 0.753 AC: 573397 AN: 761830

Other (OTH) AF: 0.745 AC: 20349 AN: 27296

GnomAD4 genome AF: 0.720 AC: 109267 AN: 151700 Hom.: 39527 Cov.: 33 AF XY: 0.720 AC XY: 53415 AN XY: 74152

African (AFR) AF: 0.645 AC: 26629 AN: 41312

American (AMR) AF: 0.787 AC: 12016 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.821 AC: 2844 AN: 3466

East Asian (EAS) AF: 0.686 AC: 3521 AN: 5136

South Asian (SAS) AF: 0.701 AC: 3385 AN: 4826

European-Finnish (FIN) AF: 0.746 AC: 7854 AN: 10534

Middle Eastern (MID) AF: 0.830 AC: 239 AN: 288

European-Non Finnish (NFE) AF: 0.746 AC: 50627 AN: 67870

Other (OTH) AF: 0.754 AC: 1587 AN: 2106

Alfa AF: 0.740 Hom.: 175075

Bravo AF: 0.725

Asia WGS AF: 0.713 AC: 2484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.6
DANN	Benign	0.37
PhyloP100		-0.19
PromoterAI		0.020	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1544224; hg19: chr1-112046540;