dbSNP rs941505: TGM1:c.-135A>T (chr14-24264066-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000560443.1(TGM1):c.-135A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,144 control chromosomes in the GnomAD database, including 1,961 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.14 ( 1961 hom., cov: 33)

Exomes 𝑓: 0.080 ( 0 hom. )

Consequence

TGM1
ENST00000560443.1 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0150

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
TGM1	ENST00000560443.1 link	c.-135A>T	5_prime_UTR_variant	Exon 1 of 2	4	ENSP00000452822.1	H0YKI6
TGM1	ENST00000560478.1 link	c.-239A>T	5_prime_UTR_variant	Exon 1 of 3	4	ENSP00000453234.1	H0YLJ6
TGM1	ENST00000561067.1 link	c.-75A>T	5_prime_UTR_variant	Exon 1 of 2	4	ENSP00000452690.1	A0A0G2JL93

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

20940

AN:

151976

Hom.:

1965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0919

Gnomad ASJ

AF:

0.0980

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.249

Gnomad FIN

AF:

0.120

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0816

Gnomad OTH

AF:

0.119

GnomAD4 exome

AF:

0.0800

AC:

AN:

Hom.:

Cov.:

AF XY:

0.118

AC XY:

AN XY:

show subpopulations

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.138

AC:

20935

AN:

152094

Hom.:

1961

Cov.:

AF XY:

0.144

AC XY:

10695

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.209

Gnomad4 AMR

AF:

0.0915

Gnomad4 ASJ

AF:

0.0980

Gnomad4 EAS

AF:

0.432

Gnomad4 SAS

AF:

0.248

Gnomad4 FIN

AF:

0.120

Gnomad4 NFE

AF:

0.0816

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.0375

Hom.:

Bravo

AF:

0.138

Asia WGS

AF:

0.308

AC:

1072

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.0

DANN

Benign

0.70

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over