rs214783

Variant names:

• chr20-2301403-A-C
• rs214783
• NM_003245.4:c.7+5333A>C

Your query was ambiguous. Multiple possible variants found:

• chr20-2301403-A-C
• chr20-2301403-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.7+5333A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.736 in 146,952 control chromosomes in the GnomAD database, including 41,788 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 0.74 (41788 hom., cov: 21)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM3	NM_003245.4	c.7+5333A>C		intron_variant	Intron 1 of 12	ENST00000381458.6	NP_003236.3
LOC105372503	XR_937203.3	n.115T>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6	c.7+5333A>C		intron_variant	Intron 1 of 12	1	NM_003245.4	ENSP00000370867.5
ENSG00000286022	ENST00000651531.1	c.65-8254A>C		intron_variant	Intron 2 of 13			ENSP00000498584.1
ENSG00000303036	ENST00000791328.1	n.22T>G		non_coding_transcript_exon_variant	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.736 AC: 108133 AN: 146836 Hom.: 41763 Cov.: 21

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.846

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.679

Gnomad NFE AF: 0.824

Gnomad OTH AF: 0.754

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

GnomAD4 genome AF: 0.736 AC: 108212 AN: 146952 Hom.: 41788 Cov.: 21 AF XY: 0.743 AC XY: 53024 AN XY: 71364

African (AFR) AF: 0.472 AC: 18519 AN: 39204

American (AMR) AF: 0.837 AC: 12229 AN: 14610

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2715 AN: 3436

East Asian (EAS) AF: 0.933 AC: 4654 AN: 4990

South Asian (SAS) AF: 0.846 AC: 3776 AN: 4464

European-Finnish (FIN) AF: 0.861 AC: 8637 AN: 10034

Middle Eastern (MID) AF: 0.676 AC: 196 AN: 290

European-Non Finnish (NFE) AF: 0.824 AC: 55233 AN: 67046

Other (OTH) AF: 0.756 AC: 1501 AN: 1986

Alfa AF: 0.773 Hom.: 5812

Bravo AF: 0.721

Asia WGS AF: 0.878 AC: 3055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	6.0
DANN	Benign	0.75
PhyloP100		0.045
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: rs214783; hg19: chr20-2282049;