Variant 14-24249309-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000359.3(TGM1):c.*4C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,612,060 control chromosomes in the GnomAD database, including 552,499 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 48257 hom., cov: 29)

Exomes 𝑓: 0.83 ( 504242 hom. )

Consequence

TGM1
NM_000359.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.265

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 14-24249309-G-A is Benign according to our data. Variant chr14-24249309-G-A is described in ClinVar as [Benign]. Clinvar id is 1342288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-24249309-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM1	NM_000359.3 linkuse as main transcript	c.*4C>T		3_prime_UTR_variant	15/15	ENST00000206765.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM1	ENST00000206765.11 linkuse as main transcript	c.*4C>T		3_prime_UTR_variant	15/15	1	NM_000359.3	P1	P22735-1
TGM1	ENST00000544573.5 linkuse as main transcript	c.*4C>T		3_prime_UTR_variant	9/9	2			P22735-2

Frequencies

GnomAD3 genomes

AF:

0.793

AC:

120408

AN:

151856

Hom.:

48238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.706

Gnomad AMI

AF:

0.928

Gnomad AMR

AF:

0.839

Gnomad ASJ

AF:

0.900

Gnomad EAS

AF:

0.572

Gnomad SAS

AF:

0.666

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.873

Gnomad NFE

AF:

0.857

Gnomad OTH

AF:

0.817

GnomAD3 exomes

AF:

0.796

AC:

199266

AN:

250274

Hom.:

80434

AF XY:

0.794

AC XY:

107493

AN XY:

135338

show subpopulations

Gnomad AFR exome

AF:

0.697

Gnomad AMR exome

AF:

0.856

Gnomad ASJ exome

AF:

0.892

Gnomad EAS exome

AF:

0.584

Gnomad SAS exome

AF:

0.675

Gnomad FIN exome

AF:

0.761

Gnomad NFE exome

AF:

0.855

Gnomad OTH exome

AF:

0.829

GnomAD4 exome

AF:

0.828

AC:

1208850

AN:

1460086

Hom.:

504242

Cov.:

AF XY:

0.825

AC XY:

599012

AN XY:

726372

show subpopulations

Gnomad4 AFR exome

AF:

0.699

Gnomad4 AMR exome

AF:

0.855

Gnomad4 ASJ exome

AF:

0.890

Gnomad4 EAS exome

AF:

0.552

Gnomad4 SAS exome

AF:

0.678

Gnomad4 FIN exome

AF:

0.766

Gnomad4 NFE exome

AF:

0.854

Gnomad4 OTH exome

AF:

0.824

GnomAD4 genome

AF:

0.793

AC:

120476

AN:

151974

Hom.:

48257

Cov.:

AF XY:

0.786

AC XY:

58342

AN XY:

74268

show subpopulations

Gnomad4 AFR

AF:

0.706

Gnomad4 AMR

AF:

0.838

Gnomad4 ASJ

AF:

0.900

Gnomad4 EAS

AF:

0.572

Gnomad4 SAS

AF:

0.667

Gnomad4 FIN

AF:

0.767

Gnomad4 NFE

AF:

0.857

Gnomad4 OTH

AF:

0.818

Alfa

AF:

0.849

Hom.:

96050

Bravo

AF:

0.797

Asia WGS

AF:

0.649

AC:

2256

AN:

3478

EpiCase

AF:

0.865

EpiControl

AF:

0.865

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Autosomal recessive congenital ichthyosis 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

7.0

DANN

Benign

0.62

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

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