20-2338077-C-G

Position:

• chr20-2338077-C-G

Variant summary

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

The NM_003245.4(TGM3):​c.1801-1777C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,042 control chromosomes in the GnomAD database, including 38,234 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 0.70 (38234 hom., cov: 32)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM3	NM_003245.4	c.1801-1777C>G		intron_variant		ENST00000381458.6	NP_003236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6	c.1801-1777C>G		intron_variant		1	NM_003245.4	ENSP00000370867	P1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106355 AN: 151926 Hom.: 38184 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.700 AC: 106460 AN: 152042 Hom.: 38234 Cov.: 32 AF XY: 0.705 AC XY: 52431 AN XY: 74332

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.702

Gnomad4 ASJ AF: 0.510

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.743

Gnomad4 FIN AF: 0.674

Gnomad4 NFE AF: 0.609

Gnomad4 OTH AF: 0.675

Alfa AF: 0.557 Hom.: 1563

Bravo AF: 0.708

Asia WGS AF: 0.782 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.39

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: rs214827; hg19: chr20-2318723;