rs2013961

Positions:

• chr20-2336844-G-T

Variant summary

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

The NM_003245.4(TGM3):​c.1800+1571G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,544 control chromosomes in the GnomAD database, including 6,210 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 0.28 (6210 hom., cov: 29)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM3	NM_003245.4	c.1800+1571G>T		intron_variant		ENST00000381458.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM3	ENST00000381458.6	c.1800+1571G>T		intron_variant		1	NM_003245.4	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42241 AN: 151426 Hom.: 6194 Cov.: 29

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.281

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42286 AN: 151544 Hom.: 6210 Cov.: 29 AF XY: 0.282 AC XY: 20890 AN XY: 74020

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.184

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.279

Alfa AF: 0.265 Hom.: 1514

Bravo AF: 0.292

Asia WGS AF: 0.332 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.88

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: rs2013961; hg19: chr20-2317490;