1-111503935-C-T

Variant names:

• chr1-111503935-C-T
• rs1544223
• ENST00000369717.8:c.108-13173G>A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.223

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 Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TMIGD3	NM_001081976.3	c.108-13173G>A		intron_variant	Intron 1 of 5		NP_001075445.1
TMIGD3	NM_001302680.2	c.108-15068G>A		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.108-13173G>A		intron_variant	Intron 1 of 5	1		ENSP00000358731.4
TMIGD3	ENST00000443498.5	c.90-15068G>A		intron_variant	Intron 1 of 4	3		ENSP00000398770.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109091 AN: 151586 Hom.: 39421 Cov.: 33

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.: 34 AF XY: 0.750 AC XY: 288409 AN XY: 384680

Gnomad4 AFR exome AF: 0.637

Gnomad4 AMR exome AF: 0.816

Gnomad4 ASJ exome AF: 0.821

Gnomad4 EAS exome AF: 0.695

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.753

Gnomad4 OTH exome AF: 0.745

GnomAD4 genome AF: 0.720 AC: 109189 AN: 151704 Hom.: 39466 Cov.: 33 AF XY: 0.720 AC XY: 53374 AN XY: 74154

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.787

Gnomad4 ASJ AF: 0.820

Gnomad4 EAS AF: 0.687

Gnomad4 SAS AF: 0.701

Gnomad4 FIN AF: 0.746

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.754

Alfa AF: 0.744 Hom.: 57554

Bravo AF: 0.724

Asia WGS AF: 0.713 AC: 2483 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 22, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29955603) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.44

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1544223; hg19: chr1-112046557;