rs2075530

Variant names:

• chr14-24263965-T-C
• rs2075530
• ENST00000560443.1:c.-34A>G

Variant summary

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

The ENST00000560443.1(TGM1):​c.-34A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0952 in 152,266 control chromosomes in the GnomAD database, including 1,095 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 0.095 (1094 hom., cov: 33)
  • Exomes 𝑓: 0.14 (1 hom.)
• Consequence: TGM1 ENST00000560443.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.234
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 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.-34A>G		5_prime_UTR_variant	Exon 1 of 2	4		ENSP00000452822.1
TGM1	ENST00000560478.1	c.-138A>G		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000453234.1
TGM1	ENST00000561067.1	c.-3+29A>G		intron_variant	Intron 1 of 1	4		ENSP00000452690.1

Frequencies

GnomAD3 genomes AF: 0.0954 AC: 14509 AN: 152112 Hom.: 1101 Cov.: 33

Gnomad AFR AF: 0.0620

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.0804

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.120

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0811

Gnomad OTH AF: 0.0879

GnomAD4 exome AF: 0.139 AC: 5 AN: 36 Hom.: 1 Cov.: 0 AF XY: 0.0833 AC XY: 2 AN XY: 24

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: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.167 AC: 5 AN: 30

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0952 AC: 14485 AN: 152230 Hom.: 1094 Cov.: 33 AF XY: 0.102 AC XY: 7592 AN XY: 74418

African (AFR) AF: 0.0618 AC: 2567 AN: 41538

American (AMR) AF: 0.0787 AC: 1204 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0804 AC: 279 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2224 AN: 5156

South Asian (SAS) AF: 0.247 AC: 1193 AN: 4828

European-Finnish (FIN) AF: 0.120 AC: 1271 AN: 10610

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0811 AC: 5516 AN: 68002

Other (OTH) AF: 0.0846 AC: 179 AN: 2116

Alfa AF: 0.0834 Hom.: 78

Bravo AF: 0.0913

Asia WGS AF: 0.288 AC: 1001 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.70
PhyloP100		0.23
PromoterAI		-0.0046	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2075530; hg19: chr14-24733171;