NM_003245.4:c.1801-1777C>G

Variant names:

• chr20-2338077-C-G
• rs214827
• NM_003245.4:c.1801-1777C>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.1801-1777C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.7 in 152,042 control chromosomes in the GnomAD database, including 38,234 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 0.70 (38234 hom., cov: 32)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384
• Publications: 0 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 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.1801-1777C>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.1801-1777C>G		intron	N/A	ENSP00000370867.5	Q08188
	ENSG00000286022	ENST00000651531.1		c.1858-1777C>G		intron	N/A	ENSP00000498584.1	A0A494C0J7

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106355 AN: 151926 Hom.: 38184 Cov.: 32

Gnomad AFR AF: 0.856

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.510

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.674

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.609

Gnomad OTH AF: 0.676

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

GnomAD4 genome AF: 0.700 AC: 106460 AN: 152042 Hom.: 38234 Cov.: 32 AF XY: 0.705 AC XY: 52431 AN XY: 74332

African (AFR) AF: 0.856 AC: 35503 AN: 41492

American (AMR) AF: 0.702 AC: 10721 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.510 AC: 1771 AN: 3470

East Asian (EAS) AF: 0.857 AC: 4421 AN: 5160

South Asian (SAS) AF: 0.743 AC: 3579 AN: 4816

European-Finnish (FIN) AF: 0.674 AC: 7115 AN: 10558

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.609 AC: 41355 AN: 67956

Other (OTH) AF: 0.675 AC: 1425 AN: 2110

Alfa AF: 0.557 Hom.: 1563

Bravo AF: 0.708

Asia WGS AF: 0.782 AC: 2714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.29
DANN	Benign	0.39
PhyloP100		-0.38
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: rs214827; hg19: chr20-2318723;