20-2320662-T-G

Variant names:

• chr20-2320662-T-G
• rs84823
• NM_003245.4:c.983+3177T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

TGM3 Gene-Disease associations (from GenCC):

• uncombable hair syndrome 2

  Inheritance: AR Classification: MODERATE, LIMITED Submitted by: PanelApp Australia, G2P
• uncombable hair syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000286022 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003245.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM3	NM_003245.4	MANE Select	c.983+3177T>G		intron	N/A	NP_003236.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM3	ENST00000381458.6	TSL:1 MANE Select	c.983+3177T>G		intron	N/A	ENSP00000370867.5	Q08188
	ENSG00000286022	ENST00000651531.1		c.1040+3177T>G		intron	N/A	ENSP00000498584.1	A0A494C0J7
	TGM3	ENST00000463090.1	TSL:3	n.363+3177T>G		intron	N/A

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

African (AFR) AF: 0.789 AC: 32730 AN: 41458

American (AMR) AF: 0.863 AC: 13190 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2742 AN: 3470

East Asian (EAS) AF: 0.956 AC: 4940 AN: 5168

South Asian (SAS) AF: 0.836 AC: 4035 AN: 4826

European-Finnish (FIN) AF: 0.813 AC: 8595 AN: 10578

Middle Eastern (MID) AF: 0.728 AC: 214 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54271 AN: 67984

Other (OTH) AF: 0.812 AC: 1710 AN: 2106

Alfa AF: 0.799 Hom.: 79565

Bravo AF: 0.813

Asia WGS AF: 0.911 AC: 3168 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.2
DANN	Benign	0.43
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs84823; hg19: chr20-2301308;