20-2340717-A-T

Variant names:

• chr20-2340717-A-T
• rs214831
• NM_003245.4:c.*136A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003245.4(TGM3):​c.*136A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TGM3 NM_003245.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.193
• Publications: 11 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM3	NM_003245.4	c.*136A>T		3_prime_UTR_variant	Exon 13 of 13	ENST00000381458.6	NP_003236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6	c.*136A>T		3_prime_UTR_variant	Exon 13 of 13	1	NM_003245.4	ENSP00000370867.5
ENSG00000286022	ENST00000651531.1	c.*136A>T		3_prime_UTR_variant	Exon 14 of 14			ENSP00000498584.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1016104 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 513300

African (AFR) AF: 0.00 AC: 0 AN: 24170

American (AMR) AF: 0.00 AC: 0 AN: 34228

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20974

East Asian (EAS) AF: 0.00 AC: 0 AN: 33784

South Asian (SAS) AF: 0.00 AC: 0 AN: 68110

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 743236

Other (OTH) AF: 0.00 AC: 0 AN: 45342

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 133373

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.85
PhyloP100		0.19

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: rs214831; hg19: chr20-2321363;