rs214831

Positions:

• chr20-2340717-A-G
• chr20-2340717-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003245.4(TGM3):​c.*136A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,165,804 control chromosomes in the GnomAD database, including 245,537 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 0.68 (35164 hom., cov: 31)
  • Exomes 𝑓: 0.64 (210373 hom.)
• Consequence: TGM3 NM_003245.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193

Genes affected

TGM3 (HGNC:11779): (transglutaminase 3) Transglutaminases are enzymes that catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds. While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent. The protein encoded by this gene consists of two polypeptide chains activated from a single precursor protein by proteolysis. The encoded protein is involved the later stages of cell envelope formation in the epidermis and hair follicle. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM3	NM_003245.4	c.*136A>G		3_prime_UTR_variant	13/13	ENST00000381458.6	NP_003236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6	c.*136A>G		3_prime_UTR_variant	13/13	1	NM_003245.4	ENSP00000370867	P1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102577 AN: 151866 Hom.: 35146 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.640 AC: 648694 AN: 1013820 Hom.: 210373 Cov.: 13 AF XY: 0.642 AC XY: 328687 AN XY: 512164

Gnomad4 AFR exome AF: 0.775

Gnomad4 AMR exome AF: 0.736

Gnomad4 ASJ exome AF: 0.507

Gnomad4 EAS exome AF: 0.866

Gnomad4 SAS exome AF: 0.759

Gnomad4 FIN exome AF: 0.677

Gnomad4 NFE exome AF: 0.611

Gnomad4 OTH exome AF: 0.650

GnomAD4 genome AF: 0.675 AC: 102641 AN: 151984 Hom.: 35164 Cov.: 31 AF XY: 0.681 AC XY: 50587 AN XY: 74294

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.501

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.659

Alfa AF: 0.618 Hom.: 58367

Bravo AF: 0.679

Asia WGS AF: 0.778 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.81

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

Other links and lift over

dbSNP: rs214831; hg19: chr20-2321363;