ENST00000560443.1:c.-135A>T

Variant names:

• chr14-24264066-T-A
• rs941505
• ENST00000560443.1:c.-135A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0150
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM1	ENST00000560443.1	c.-135A>T		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000452822.1
TGM1	ENST00000560478.1	c.-239A>T		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000453234.1
TGM1	ENST00000561067.1	c.-75A>T		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000452690.1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 20940 AN: 151976 Hom.: 1965 Cov.: 33

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: 4 AN: 50 Hom.: 0 Cov.: 0 AF XY: 0.118 AC XY: 4 AN XY: 34

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 4 AN: 36

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.138 AC: 20935 AN: 152094 Hom.: 1961 Cov.: 33 AF XY: 0.144 AC XY: 10695 AN XY: 74344

African (AFR) AF: 0.209 AC: 8667 AN: 41474

American (AMR) AF: 0.0915 AC: 1400 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3470

East Asian (EAS) AF: 0.432 AC: 2222 AN: 5142

South Asian (SAS) AF: 0.248 AC: 1192 AN: 4806

European-Finnish (FIN) AF: 0.120 AC: 1267 AN: 10592

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0816 AC: 5550 AN: 67996

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.0375 Hom.: 28

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
PhyloP100		-0.015
PromoterAI		-0.0023	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs941505; hg19: chr14-24733272;