20-2306058-T-G

Variant names:

• chr20-2306058-T-G
• rs214799
• NM_003245.4:c.8-3599T>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.8-3599T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 151,936 control chromosomes in the GnomAD database, including 44,027 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 0.75 (44027 hom., cov: 31)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.424
• Publications: 2 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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• uncombable hair syndrome 2

  Inheritance: AR Classification: LIMITED Submitted by: G2P

ENSG00000286022 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM3	NM_003245.4	c.8-3599T>G		intron_variant	Intron 1 of 12	ENST00000381458.6	NP_003236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6	c.8-3599T>G		intron_variant	Intron 1 of 12	1	NM_003245.4	ENSP00000370867.5
ENSG00000286022	ENST00000651531.1	c.65-3599T>G		intron_variant	Intron 2 of 13			ENSP00000498584.1

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113504 AN: 151818 Hom.: 44007 Cov.: 31

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.841

Gnomad FIN AF: 0.859

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.748 AC: 113579 AN: 151936 Hom.: 44027 Cov.: 31 AF XY: 0.753 AC XY: 55945 AN XY: 74272

African (AFR) AF: 0.520 AC: 21505 AN: 41378

American (AMR) AF: 0.839 AC: 12808 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2791 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4815 AN: 5160

South Asian (SAS) AF: 0.841 AC: 4055 AN: 4822

European-Finnish (FIN) AF: 0.859 AC: 9077 AN: 10566

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55948 AN: 67960

Other (OTH) AF: 0.763 AC: 1606 AN: 2104

Alfa AF: 0.770 Hom.: 6473

Bravo AF: 0.735

Asia WGS AF: 0.876 AC: 3047 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	7.3
DANN	Benign	0.87
PhyloP100		0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs214799; hg19: chr20-2286704;