chr14-24249326-C-G
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000359.3(TGM1):āc.2441G>Cā(p.Arg814Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
TGM1
NM_000359.3 missense
NM_000359.3 missense
Scores
3
10
5
Clinical Significance
Conservation
PhyloP100: 3.59
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TGM1 | NM_000359.3 | c.2441G>C | p.Arg814Pro | missense_variant | 15/15 | ENST00000206765.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TGM1 | ENST00000206765.11 | c.2441G>C | p.Arg814Pro | missense_variant | 15/15 | 1 | NM_000359.3 | P1 | |
TGM1 | ENST00000544573.5 | c.1115G>C | p.Arg372Pro | missense_variant | 9/9 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1461354Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 726994
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1461354
Hom.:
Cov.:
34
AF XY:
AC XY:
0
AN XY:
726994
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 17, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
D;.
Vest4
MutPred
Loss of methylation at R814 (P = 0.0151);.;
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at