chr20-2320662-T-G

Position:

• chr20-2320662-T-G

Variant summary

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

The NM_003245.4(TGM3):​c.983+3177T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 152,074 control chromosomes in the GnomAD database, including 49,966 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 0.81 (49966 hom., cov: 31)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.155

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM3	NM_003245.4	c.983+3177T>G		intron_variant		ENST00000381458.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM3	ENST00000381458.6	c.983+3177T>G		intron_variant		1	NM_003245.4	P1
TGM3	ENST00000463090.1	n.363+3177T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.810 AC: 123029 AN: 151956 Hom.: 49911 Cov.: 31

Gnomad AFR AF: 0.789

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.863

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.813

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.810

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

GnomAD4 genome AF: 0.810 AC: 123142 AN: 152074 Hom.: 49966 Cov.: 31 AF XY: 0.810 AC XY: 60230 AN XY: 74330

Gnomad4 AFR AF: 0.789

Gnomad4 AMR AF: 0.863

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.813

Gnomad4 NFE AF: 0.798

Gnomad4 OTH AF: 0.812

Alfa AF: 0.798 Hom.: 62264

Bravo AF: 0.813

Asia WGS AF: 0.911 AC: 3168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.43

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: rs84823; hg19: chr20-2301308;