rs214831

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr20-2340717-A-G
• chr20-2340717-A-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.*136A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 1,165,804 control chromosomes in the GnomAD database, including 245,537 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 0.68 (35164 hom., cov: 31)
  • Exomes 𝑓: 0.64 (210373 hom.)
• 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 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 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.*136A>G		3_prime_UTR	Exon 13 of 13	NP_003236.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM3	ENST00000381458.6	TSL:1 MANE Select	c.*136A>G		3_prime_UTR	Exon 13 of 13	ENSP00000370867.5	Q08188
	ENSG00000286022	ENST00000651531.1		c.*136A>G		3_prime_UTR	Exon 14 of 14	ENSP00000498584.1	A0A494C0J7

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102577 AN: 151866 Hom.: 35146 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.694

Gnomad ASJ AF: 0.501

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.658

GnomAD4 exome AF: 0.640 AC: 648694 AN: 1013820 Hom.: 210373 Cov.: 13 AF XY: 0.642 AC XY: 328687 AN XY: 512164

African (AFR) AF: 0.775 AC: 18688 AN: 24118

American (AMR) AF: 0.736 AC: 25170 AN: 34210

Ashkenazi Jewish (ASJ) AF: 0.507 AC: 10605 AN: 20930

East Asian (EAS) AF: 0.866 AC: 29236 AN: 33758

South Asian (SAS) AF: 0.759 AC: 51636 AN: 68066

European-Finnish (FIN) AF: 0.677 AC: 28092 AN: 41500

Middle Eastern (MID) AF: 0.642 AC: 3001 AN: 4678

European-Non Finnish (NFE) AF: 0.611 AC: 452849 AN: 741302

Other (OTH) AF: 0.650 AC: 29417 AN: 45258

GnomAD4 genome AF: 0.675 AC: 102641 AN: 151984 Hom.: 35164 Cov.: 31 AF XY: 0.681 AC XY: 50587 AN XY: 74294

African (AFR) AF: 0.766 AC: 31735 AN: 41452

American (AMR) AF: 0.695 AC: 10614 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.501 AC: 1737 AN: 3468

East Asian (EAS) AF: 0.855 AC: 4402 AN: 5146

South Asian (SAS) AF: 0.755 AC: 3640 AN: 4820

European-Finnish (FIN) AF: 0.679 AC: 7177 AN: 10576

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41371 AN: 67936

Other (OTH) AF: 0.659 AC: 1388 AN: 2106

Alfa AF: 0.630 Hom.: 133373

Bravo AF: 0.679

Asia WGS AF: 0.778 AC: 2702 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.2
DANN	Benign	0.81
PhyloP100		0.19
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: rs214831; hg19: chr20-2321363;