20-2301324-G-A

Variant names:

• chr20-2301324-G-A
• rs214782
• NM_003245.4:c.7+5254G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003245.4(TGM3):​c.7+5254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 149,486 control chromosomes in the GnomAD database, including 42,339 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 0.73 (42339 hom., cov: 23)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• Publications: 17 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 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.7+5254G>A		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.7+5254G>A		intron	N/A	ENSP00000370867.5
	ENSG00000286022	ENST00000651531.1		c.65-8333G>A		intron	N/A	ENSP00000498584.1
	ENSG00000303036	ENST00000791328.1		n.101C>T		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.735 AC: 109749 AN: 149368 Hom.: 42313 Cov.: 23

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.836

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.860

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.751

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

GnomAD4 genome AF: 0.735 AC: 109829 AN: 149486 Hom.: 42339 Cov.: 23 AF XY: 0.741 AC XY: 53906 AN XY: 72726

African (AFR) AF: 0.472 AC: 19037 AN: 40366

American (AMR) AF: 0.836 AC: 12507 AN: 14958

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2733 AN: 3458

East Asian (EAS) AF: 0.933 AC: 4715 AN: 5056

South Asian (SAS) AF: 0.845 AC: 3900 AN: 4618

European-Finnish (FIN) AF: 0.860 AC: 8790 AN: 10226

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.824 AC: 55630 AN: 67544

Other (OTH) AF: 0.754 AC: 1554 AN: 2062

Alfa AF: 0.798 Hom.: 73242

Bravo AF: 0.721

Asia WGS AF: 0.878 AC: 3055 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	7.2
DANN	Benign	0.51
PhyloP100		0.26
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: rs214782; hg19: chr20-2281970;