rs398122901

Variant names:

• chr14-24262048-T-A
• rs398122901
• NM_000359.3:c.305A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-24262048-T-A
• chr14-24262048-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The NM_000359.3(TGM1):​c.305A>T​(p.Asp102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGM1 NM_000359.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 1.42

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 14-24262048-T-A is Pathogenic according to our data. Variant chr14-24262048-T-A is described in ClinVar as [Pathogenic]. Clinvar id is 39525.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr14-24262048-T-A is described in UniProt as null. Variant chr14-24262048-T-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM1	NM_000359.3	c.305A>T	p.Asp102Val	missense_variant	Exon 2 of 15	ENST00000206765.11	NP_000350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM1	ENST00000206765.11	c.305A>T	p.Asp102Val	missense_variant	Exon 2 of 15	1	NM_000359.3	ENSP00000206765.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Autosomal recessive congenital ichthyosis 1 Pathogenic:1

Aug 01, 2001

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.24
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.27	T;T
Eigen	Benign	-0.029
Eigen_PC	Benign	0.065
FATHMM_MKL	Benign	0.70	D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.71	D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.23	N;D
REVEL	Uncertain	0.57
Sift	Uncertain	0.023	D;D
Sift4G	Benign	0.090	T;T
Polyphen		0.72	P;.
Vest4		0.89
MutPred		0.75		Gain of sheet (P = 0.0028);Gain of sheet (P = 0.0028);
MVP		0.97
MPC		0.67
ClinPred		0.68	D
GERP RS		3.5
Varity_R		0.15
gMVP		0.74

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

LitVar

Other links and lift over

dbSNP: rs398122901; hg19: chr14-24731254;