rs35755034

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000359.3(TGM1):c.726G>A(p.Glu242Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 1,614,194 control chromosomes in the GnomAD database, including 1,103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 292 hom., cov: 33)

Exomes 𝑓: 0.025 ( 811 hom. )

Consequence

TGM1
NM_000359.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.133

Publications

9 publications found

Variant links:

Genes affected

TGM1 (HGNC:11777): (transglutaminase 1) The protein encoded by this gene is a membrane protein that catalyzes the addition of an alkyl group from an akylamine to a glutamine residue of a protein, forming an alkylglutamine in the protein. This protein alkylation leads to crosslinking of proteins and catenation of polyamines to proteins. This gene contains either one or two copies of a 22 nt repeat unit in its 3' UTR. Mutations in this gene have been associated with autosomal recessive lamellar ichthyosis (LI) and nonbullous congenital ichthyosiform erythroderma (NCIE). [provided by RefSeq, Jul 2008]

TGM1 Gene-Disease associations (from GenCC):

autosomal recessive congenital ichthyosis 1
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Genomics England PanelApp, Myriad Women’s Health, G2P
acral self-healing collodion baby
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
bathing suit ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
congenital non-bullous ichthyosiform erythroderma
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
self-healing collodion baby
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

TGM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 14-24260481-C-T is Benign according to our data. Variant chr14-24260481-C-T is described in ClinVar as Benign. ClinVar VariationId is 255942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.133 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000359.3. 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
	TGM1	NM_000359.3	MANE Select	c.726G>A	p.Glu242Glu	synonymous	Exon 4 of 15	NP_000350.1	P22735-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TGM1	ENST00000206765.11	TSL:1 MANE Select	c.726G>A	p.Glu242Glu	synonymous	Exon 4 of 15	ENSP00000206765.6	P22735-1
TGM1	ENST00000879556.1		c.726G>A	p.Glu242Glu	synonymous	Exon 3 of 14	ENSP00000549615.1
TGM1	ENST00000544573.5	TSL:2	c.-29+1646G>A		intron	N/A	ENSP00000439446.1	P22735-2

Frequencies

GnomAD3 genomes

AF:

0.0485

AC:

7375

AN:

152188

Hom.:

291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0292

Gnomad ASJ

AF:

0.0429

Gnomad EAS

AF:

0.0662

Gnomad SAS

AF:

0.0598

Gnomad FIN

AF:

0.0335

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0200

Gnomad OTH

AF:

0.0392

GnomAD2 exomes

AF:

0.0368

AC:

9257

AN:

251412

AF XY:

0.0377

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0149

Gnomad ASJ exome

AF:

0.0445

Gnomad EAS exome

AF:

0.0795

Gnomad FIN exome

AF:

0.0338

Gnomad NFE exome

AF:

0.0191

Gnomad OTH exome

AF:

0.0367

GnomAD4 exome

AF:

0.0254

AC:

37142

AN:

1461888

Hom.:

811

Cov.:

AF XY:

0.0265

AC XY:

19292

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.107

AC:

3569

AN:

33480

American (AMR)

AF:

0.0165

AC:

738

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0448

AC:

1171

AN:

26136

East Asian (EAS)

AF:

0.0619

AC:

2458

AN:

39700

South Asian (SAS)

AF:

0.0635

AC:

5481

AN:

86258

European-Finnish (FIN)

AF:

0.0323

AC:

1728

AN:

53418

Middle Eastern (MID)

AF:

0.0505

AC:

291

AN:

5768

European-Non Finnish (NFE)

AF:

0.0178

AC:

19798

AN:

1112008

Other (OTH)

AF:

0.0316

AC:

1908

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

2619

5238

7858

10477

13096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

870

1740

2610

3480

4350

<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:

0.0485

AC:

7384

AN:

152306

Hom.:

292

Cov.:

AF XY:

0.0499

AC XY:

3720

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.104

AC:

4338

AN:

41550

American (AMR)

AF:

0.0291

AC:

446

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0429

AC:

149

AN:

3470

East Asian (EAS)

AF:

0.0664

AC:

344

AN:

5184

South Asian (SAS)

AF:

0.0605

AC:

292

AN:

4828

European-Finnish (FIN)

AF:

0.0335

AC:

356

AN:

10624

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0200

AC:

1358

AN:

68024

Other (OTH)

AF:

0.0388

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

356

712

1069

1425

1781

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0326

Hom.:

264

Bravo

AF:

0.0502

Asia WGS

AF:

0.0500

AC:

172

AN:

3478

EpiCase

AF:

0.0204

EpiControl

AF:

0.0207

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Autosomal recessive congenital ichthyosis 1 (3)

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

6.5

(source)

DANN

Benign

0.87

PhyloP100

0.13

PromoterAI

-0.038

Neutral

(source)

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over