rs941505

Positions:

• chr14-24264066-T-A
• chr14-24264066-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
		n.24264066T>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM1	ENST00000560443.1	c.-135A>T		5_prime_UTR_variant	1/2	4		ENSP00000452822.1
TGM1	ENST00000560478.1	c.-239A>T		5_prime_UTR_variant	1/3	4		ENSP00000453234.1
TGM1	ENST00000561067.1	c.-75A>T		5_prime_UTR_variant	1/2	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

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.: 33 AF XY: 0.144 AC XY: 10695 AN XY: 74344

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.: 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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs941505; hg19: chr14-24733272;