20-2336844-G-T

Variant names:

• chr20-2336844-G-T
• rs2013961
• NM_003245.4:c.1800+1571G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003245.4(TGM3):​c.1800+1571G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,544 control chromosomes in the GnomAD database, including 6,210 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 0.28 (6210 hom., cov: 29)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0620
• Publications: 4 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM3	NM_003245.4	c.1800+1571G>T		intron_variant	Intron 11 of 12	ENST00000381458.6	NP_003236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6	c.1800+1571G>T		intron_variant	Intron 11 of 12	1	NM_003245.4	ENSP00000370867.5
ENSG00000286022	ENST00000651531.1	c.1857+1571G>T		intron_variant	Intron 12 of 13			ENSP00000498584.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42241 AN: 151426 Hom.: 6194 Cov.: 29

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.279 AC: 42286 AN: 151544 Hom.: 6210 Cov.: 29 AF XY: 0.282 AC XY: 20890 AN XY: 74020

African (AFR) AF: 0.316 AC: 13037 AN: 41264

American (AMR) AF: 0.365 AC: 5561 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 637 AN: 3466

East Asian (EAS) AF: 0.457 AC: 2334 AN: 5102

South Asian (SAS) AF: 0.328 AC: 1575 AN: 4796

European-Finnish (FIN) AF: 0.241 AC: 2536 AN: 10508

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15783 AN: 67876

Other (OTH) AF: 0.279 AC: 586 AN: 2104

Alfa AF: 0.265 Hom.: 1514

Bravo AF: 0.292

Asia WGS AF: 0.332 AC: 1156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.062
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: rs2013961; hg19: chr20-2317490;