NM_003245.4:c.8-5527G>C

Variant names:

• chr20-2304130-G-C
• rs10485599
• NM_003245.4:c.8-5527G>C

Variant summary

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

The NM_003245.4(TGM3):​c.8-5527G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0992 in 152,146 control chromosomes in the GnomAD database, including 2,547 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 0.099 (2547 hom., cov: 32)
• Consequence: TGM3 NM_003245.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0850
• 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

  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 = 0.338 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.8-5527G>C		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.8-5527G>C		intron	N/A	ENSP00000370867.5
	ENSG00000286022	ENST00000651531.1		c.65-5527G>C		intron	N/A	ENSP00000498584.1

Frequencies

GnomAD3 genomes AF: 0.0991 AC: 15073 AN: 152028 Hom.: 2545 Cov.: 32

Gnomad AFR AF: 0.343

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0431

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00113

Gnomad OTH AF: 0.0741

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

GnomAD4 genome AF: 0.0992 AC: 15091 AN: 152146 Hom.: 2547 Cov.: 32 AF XY: 0.0951 AC XY: 7075 AN XY: 74394

African (AFR) AF: 0.342 AC: 14191 AN: 41446

American (AMR) AF: 0.0430 AC: 657 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00113 AC: 77 AN: 68006

Other (OTH) AF: 0.0733 AC: 155 AN: 2114

Alfa AF: 0.0779 Hom.: 189

Bravo AF: 0.114

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.81
DANN	Benign	0.63
PhyloP100		-0.085
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: rs10485599; hg19: chr20-2284776;