14-24259088-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000359.3(TGM1):c.1146C>A(p.Gly382Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,613,700 control chromosomes in the GnomAD database, including 29,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2501 hom., cov: 33)

Exomes 𝑓: 0.19 ( 26989 hom. )

Consequence

TGM1
NM_000359.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -2.34

Publications

22 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: G2P, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, PanelApp Australia, Genomics England PanelApp
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 14-24259088-G-T is Benign according to our data. Variant chr14-24259088-G-T is described in ClinVar as Benign. ClinVar VariationId is 255941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.34 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGM1	NM_000359.3	MANE Select	c.1146C>A	p.Gly382Gly	synonymous	Exon 7 of 15	NP_000350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TGM1	ENST00000206765.11	TSL:1 MANE Select	c.1146C>A	p.Gly382Gly	synonymous	Exon 7 of 15	ENSP00000206765.6
TGM1	ENST00000559136.1	TSL:5	c.219C>A	p.Gly73Gly	synonymous	Exon 3 of 7	ENSP00000453337.1
TGM1	ENST00000544573.5	TSL:2	c.-28-700C>A		intron	N/A	ENSP00000439446.1

Frequencies

GnomAD3 genomes

AF:

0.178

AC:

27066

AN:

152036

Hom.:

2502

Cov.:

show subpopulations

Gnomad AFR

AF:

0.177

Gnomad AMI

AF:

0.209

Gnomad AMR

AF:

0.161

Gnomad ASJ

AF:

0.172

Gnomad EAS

AF:

0.0824

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.199

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.168

AC:

42084

AN:

250736

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.0791

Gnomad FIN exome

AF:

0.151

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.189

AC:

276316

AN:

1461546

Hom.:

26989

Cov.:

AF XY:

0.188

AC XY:

136342

AN XY:

727062

show subpopulations

African (AFR)

AF:

0.176

AC:

5878

AN:

33466

American (AMR)

AF:

0.170

AC:

7590

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.175

AC:

4580

AN:

26130

East Asian (EAS)

AF:

0.0704

AC:

2794

AN:

39698

South Asian (SAS)

AF:

0.140

AC:

12109

AN:

86244

European-Finnish (FIN)

AF:

0.157

AC:

8368

AN:

53326

Middle Eastern (MID)

AF:

0.145

AC:

838

AN:

5762

European-Non Finnish (NFE)

AF:

0.201

AC:

223316

AN:

1111836

Other (OTH)

AF:

0.180

AC:

10843

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

13165

26329

39494

52658

65823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7730

15460

23190

30920

38650

<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:

0.178

AC:

27076

AN:

152154

Hom.:

2501

Cov.:

AF XY:

0.172

AC XY:

12769

AN XY:

74398

show subpopulations

African (AFR)

AF:

0.176

AC:

7312

AN:

41486

American (AMR)

AF:

0.161

AC:

2461

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

598

AN:

3470

East Asian (EAS)

AF:

0.0822

AC:

426

AN:

5184

South Asian (SAS)

AF:

0.127

AC:

610

AN:

4818

European-Finnish (FIN)

AF:

0.147

AC:

1558

AN:

10596

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.199

AC:

13505

AN:

67986

Other (OTH)

AF:

0.178

AC:

375

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1148

2296

3445

4593

5741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

298

596

894

1192

1490

<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:

0.178

Hom.:

3413

Bravo

AF:

0.180

Asia WGS

AF:

0.111

AC:

385

AN:

3478

EpiCase

AF:

0.187

EpiControl

AF:

0.188

ClinVar

ClinVar submissions as Germline

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 (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.60

(source)

DANN

Benign

0.72

PhyloP100

-2.3

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over