20-2319962-C-T

Variant names:

• chr20-2319962-C-T
• rs84825
• NM_003245.4:c.983+2477C>T

Variant summary

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

The NM_003245.4(TGM3):​c.983+2477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,172 control chromosomes in the GnomAD database, including 38,603 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 0.69 (38603 hom., cov: 33)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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]

ENSG00000286022 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• 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 rank	MANE	Protein	UniProt
TGM3	NM_003245.4	c.983+2477C>T		intron_variant	Intron 7 of 12	ENST00000381458.6	NP_003236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6	c.983+2477C>T		intron_variant	Intron 7 of 12	1	NM_003245.4	ENSP00000370867.5
ENSG00000286022	ENST00000651531.1	c.1040+2477C>T		intron_variant	Intron 8 of 13			ENSP00000498584.1
TGM3	ENST00000463090.1	n.363+2477C>T		intron_variant	Intron 3 of 3	3

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105077 AN: 152054 Hom.: 38588 Cov.: 33

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.691 AC: 105118 AN: 152172 Hom.: 38603 Cov.: 33 AF XY: 0.696 AC XY: 51794 AN XY: 74394

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.808

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.956

Gnomad4 SAS AF: 0.825

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.709

Alfa AF: 0.763 Hom.: 41515

Bravo AF: 0.679

Asia WGS AF: 0.876 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.73

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: rs84825; hg19: chr20-2300608;