NM_000359.3:c.1552G>C

Variant names:

• chr14-24255457-C-G
• NM_000359.3:c.1552G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_000359.3(TGM1):​c.1552G>C​(p.Val518Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V518M) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TGM1 NM_000359.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.624

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr14-24255457-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM1	NM_000359.3	c.1552G>C	p.Val518Leu	missense_variant	Exon 11 of 15	ENST00000206765.11	NP_000350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM1	ENST00000206765.11	c.1552G>C	p.Val518Leu	missense_variant	Exon 11 of 15	1	NM_000359.3	ENSP00000206765.6
TGM1	ENST00000544573.5	c.226G>C	p.Val76Leu	missense_variant	Exon 5 of 9	2		ENSP00000439446.1
TGM1	ENST00000559136.1	c.625G>C	p.Val209Leu	missense_variant	Exon 7 of 7	5		ENSP00000453337.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.012	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;.;T
Eigen	Benign	0.013
Eigen_PC	Benign	0.066
FATHMM_MKL	Uncertain	0.76	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.52	D;D;T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	1.8	L;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Uncertain	0.29
Sift	Benign	0.066	T;T;D
Sift4G	Benign	0.13	T;T;.
Polyphen		0.65	P;.;.
Vest4		0.30
MutPred		0.69		Loss of methylation at K514 (P = 0.0738);.;.;
MVP		0.89
MPC		0.37
ClinPred		0.72	D
GERP RS		4.9
Varity_R		0.24
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-24724663;