NM_000359.3:c.1146C>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 255941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-24259088-G-T is described in Lovd as [Benign].

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM1	NM_000359.3 link	c.1146C>A	p.Gly382Gly	synonymous_variant	Exon 7 of 15	ENST00000206765.11	NP_000350.1	P22735-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TGM1	ENST00000206765.11 link	c.1146C>A	p.Gly382Gly	synonymous_variant	Exon 7 of 15	1	NM_000359.3	ENSP00000206765.6	P22735-1
TGM1	ENST00000559136.1 link	c.219C>A	p.Gly73Gly	synonymous_variant	Exon 3 of 7	5		ENSP00000453337.1	H0YLT9
TGM1	ENST00000544573.5 link	c.-28-700C>A		intron_variant	Intron 2 of 8	2		ENSP00000439446.1	P22735-2

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

GnomAD3 exomes

AF:

0.168

AC:

42084

AN:

250736

Hom.:

3685

AF XY:

0.167

AC XY:

22700

AN XY:

135602

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 SAS exome

AF:

0.137

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

Gnomad4 AFR exome

AF:

0.176

Gnomad4 AMR exome

AF:

0.170

Gnomad4 ASJ exome

AF:

0.175

Gnomad4 EAS exome

AF:

0.0704

Gnomad4 SAS exome

AF:

0.140

Gnomad4 FIN exome

AF:

0.157

Gnomad4 NFE exome

AF:

0.201

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.178

AC:

27076

AN:

152154

Hom.:

2501

Cov.:

AF XY:

0.172

AC XY:

12769

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.161

Gnomad4 ASJ

AF:

0.172

Gnomad4 EAS

AF:

0.0822

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.199

Gnomad4 OTH

AF:

0.178

Alfa

AF:

0.179

Hom.:

3137

Bravo

AF:

0.180

Asia WGS

AF:

0.111

AC:

385

AN:

3478

EpiCase

AF:

0.187

EpiControl

AF:

0.188

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Autosomal recessive congenital ichthyosis 1

Benign:3

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Nov 20, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.60

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over