20-2303794-A-G

Variant names:

• chr20-2303794-A-G
• rs3895160
• NM_003245.4:c.8-5863A>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.8-5863A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 148,532 control chromosomes in the GnomAD database, including 2,894 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 0.11 (2894 hom., cov: 32)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• 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

  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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.367 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM3	NM_003245.4	MANE Select	c.8-5863A>G		intron	N/A	NP_003236.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM3	ENST00000381458.6	TSL:1 MANE Select	c.8-5863A>G		intron	N/A	ENSP00000370867.5
	ENSG00000286022	ENST00000651531.1		c.65-5863A>G		intron	N/A	ENSP00000498584.1

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16204 AN: 148412 Hom.: 2889 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0524

Gnomad ASJ AF: 0.000896

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00195

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0308

Gnomad NFE AF: 0.00150

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.109 AC: 16239 AN: 148532 Hom.: 2894 Cov.: 32 AF XY: 0.104 AC XY: 7579 AN XY: 72634

African (AFR) AF: 0.372 AC: 15163 AN: 40712

American (AMR) AF: 0.0522 AC: 783 AN: 14994

Ashkenazi Jewish (ASJ) AF: 0.000896 AC: 3 AN: 3350

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00174 AC: 8 AN: 4604

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10364

Middle Eastern (MID) AF: 0.0331 AC: 9 AN: 272

European-Non Finnish (NFE) AF: 0.00150 AC: 99 AN: 66180

Other (OTH) AF: 0.0856 AC: 174 AN: 2032

Alfa AF: 0.139 Hom.: 463

Bravo AF: 0.124

Asia WGS AF: 0.0220 AC: 77 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.4
DANN	Benign	0.60
PhyloP100		-0.33
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: rs3895160; hg19: chr20-2284440;