chr14-24249326-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000359.3(TGM1):ā€‹c.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

Scores

3
10
5

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.59
Variant links:
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]

Genome browser will be placed here

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
TGM1NM_000359.3 linkuse as main transcriptc.2441G>C p.Arg814Pro missense_variant 15/15 ENST00000206765.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGM1ENST00000206765.11 linkuse as main transcriptc.2441G>C p.Arg814Pro missense_variant 15/151 NM_000359.3 P1P22735-1
TGM1ENST00000544573.5 linkuse as main transcriptc.1115G>C p.Arg372Pro missense_variant 9/92 P22735-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1461354
Hom.:
0
Cov.:
34
AF XY:
0.00
AC XY:
0
AN XY:
726994
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 providedclinical testingNatera, Inc.Apr 17, 2020- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.090
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T;.
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.87
D
M_CAP
Uncertain
0.19
D
MetaRNN
Uncertain
0.44
T;T
MetaSVM
Uncertain
-0.063
T
MutationAssessor
Benign
1.4
L;.
MutationTaster
Benign
0.75
D;D
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-0.39
N;N
REVEL
Uncertain
0.30
Sift
Pathogenic
0.0
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;.
Vest4
0.47
MutPred
0.26
Loss of methylation at R814 (P = 0.0151);.;
MVP
0.96
MPC
1.1
ClinPred
0.85
D
GERP RS
5.0
Varity_R
0.32
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs747705778; hg19: chr14-24718532; COSMIC: COSV52863736; COSMIC: COSV52863736; API