20-2319962-C-T

Variant names:

• chr20-2319962-C-T
• rs84825
• NM_003245.4:c.983+2477C>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.983+2477C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 152,172 control chromosomes in the GnomAD database, including 38,603 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 0.69 (38603 hom., cov: 33)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 1 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 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.983+2477C>T		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.983+2477C>T		intron	N/A	ENSP00000370867.5	Q08188
	ENSG00000286022	ENST00000651531.1		c.1040+2477C>T		intron	N/A	ENSP00000498584.1	A0A494C0J7
	TGM3	ENST00000463090.1	TSL:3	n.363+2477C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.691 AC: 105077 AN: 152054 Hom.: 38588 Cov.: 33

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.807

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.956

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.706

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

GnomAD4 genome AF: 0.691 AC: 105118 AN: 152172 Hom.: 38603 Cov.: 33 AF XY: 0.696 AC XY: 51794 AN XY: 74394

African (AFR) AF: 0.417 AC: 17325 AN: 41500

American (AMR) AF: 0.808 AC: 12349 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2615 AN: 3472

East Asian (EAS) AF: 0.956 AC: 4953 AN: 5180

South Asian (SAS) AF: 0.825 AC: 3983 AN: 4826

European-Finnish (FIN) AF: 0.805 AC: 8511 AN: 10576

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52973 AN: 68006

Other (OTH) AF: 0.709 AC: 1501 AN: 2116

Alfa AF: 0.751 Hom.: 52823

Bravo AF: 0.679

Asia WGS AF: 0.876 AC: 3044 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.2
DANN	Benign	0.73
PhyloP100		0.13
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: rs84825; hg19: chr20-2300608;