rs214803

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003245.4(TGM3):c.38C>A(p.Thr13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,613,856 control chromosomes in the GnomAD database, including 535,774 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.73 ( 42987 hom., cov: 32)

Exomes 𝑓: 0.82 ( 492787 hom. )

Consequence

TGM3
NM_003245.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.43

Publications

37 publications found

Variant links:

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

TGM3 links:

ENSG00000286022 (HGNC:):

ENSG00000286022 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.677294E-7).

BP6

Variant 20-2309687-C-A is Benign according to our data. Variant chr20-2309687-C-A is described in ClinVar as Benign. ClinVar VariationId is 3060440.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM3	NM_003245.4 link	c.38C>A	p.Thr13Lys	missense_variant	Exon 2 of 13	ENST00000381458.6	NP_003236.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM3	ENST00000381458.6 link	c.38C>A	p.Thr13Lys	missense_variant	Exon 2 of 13	1	NM_003245.4	ENSP00000370867.5
ENSG00000286022	ENST00000651531.1 link	c.95C>A	p.Thr32Lys	missense_variant	Exon 3 of 14			ENSP00000498584.1

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111525

AN:

151970

Hom.:

42964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.838

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.840

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.823

Gnomad OTH

AF:

0.756

GnomAD2 exomes

AF:

0.819

AC:

205989

AN:

251430

AF XY:

0.823

show subpopulations

Gnomad AFR exome

AF:

0.462

Gnomad AMR exome

AF:

0.893

Gnomad ASJ exome

AF:

0.779

Gnomad EAS exome

AF:

0.933

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.821

Gnomad OTH exome

AF:

0.804

GnomAD4 exome

AF:

0.818

AC:

1196237

AN:

1461768

Hom.:

492787

Cov.:

AF XY:

0.819

AC XY:

595705

AN XY:

727182

show subpopulations

African (AFR)

AF:

0.455

AC:

15235

AN:

33476

American (AMR)

AF:

0.887

AC:

39648

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.780

AC:

20377

AN:

26132

East Asian (EAS)

AF:

0.946

AC:

37542

AN:

39700

South Asian (SAS)

AF:

0.835

AC:

72029

AN:

86256

European-Finnish (FIN)

AF:

0.859

AC:

45903

AN:

53420

Middle Eastern (MID)

AF:

0.729

AC:

4172

AN:

5722

European-Non Finnish (NFE)

AF:

0.821

AC:

912836

AN:

1111948

Other (OTH)

AF:

0.803

AC:

48495

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

12257

24514

36771

49028

61285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20902

41804

62706

83608

104510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.734

AC:

111603

AN:

152088

Hom.:

42987

Cov.:

AF XY:

0.740

AC XY:

55046

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.471

AC:

19514

AN:

41440

American (AMR)

AF:

0.839

AC:

12818

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.792

AC:

2747

AN:

3470

East Asian (EAS)

AF:

0.934

AC:

4825

AN:

5166

South Asian (SAS)

AF:

0.839

AC:

4051

AN:

4826

European-Finnish (FIN)

AF:

0.859

AC:

9104

AN:

10598

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.823

AC:

55964

AN:

67984

Other (OTH)

AF:

0.758

AC:

1601

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1327

2654

3981

5308

6635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.793

Hom.:

199322

Bravo

AF:

0.720

TwinsUK

AF:

0.821

AC:

3044

ALSPAC

AF:

0.822

AC:

3169

ESP6500AA

AF:

0.485

AC:

2137

ESP6500EA

AF:

0.821

AC:

7058

ExAC

AF:

0.810

AC:

98372

Asia WGS

AF:

0.877

AC:

3052

AN:

3478

EpiCase

AF:

0.813

EpiControl

AF:

0.806

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TGM3-related disorder

Benign:1

Apr 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.0080

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.16

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.10

MetaRNN

Benign

9.7e-7

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.69

PhyloP100

-2.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.21

REVEL

Benign

0.17

Sift

Benign

0.69

Sift4G

Benign

0.64

Polyphen

0.73

Vest4

0.037

MPC

0.096

ClinPred

0.0052

GERP RS

-1.1

Varity_R

0.17

gMVP

0.42

Mutation Taster

=94/6

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over