rs10485599

chr20-2304130-G-C

Variant summary

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

The NM_003245.4(TGM3):c.8-5527G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 152,146 control chromosomes in the GnomAD database, including 2,547 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 0.099 (2547 hom., cov: 32)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM3	NM_003245.4	c.8-5527G>C		intron_variant		ENST00000381458.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM3	ENST00000381458.6	c.8-5527G>C		intron_variant		1	NM_003245.4	P1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15073 AN: 152028 Hom.: 2545 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0992 AC: 15091 AN: 152146 Hom.: 2547 Cov.: 32 AF XY: 0.0951 AC XY: 7075 AN XY: 74394

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.0430

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00113

Gnomad4 OTH AF: 0.0733

Alfa AF: 0.0779 Hom.: 189

Bravo AF: 0.114

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.81
Dann	Benign	0.63

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: rs10485599; hg19: chr20-2284776;