chr14-24249391-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000359.3(TGM1):​c.2376T>A​(p.Asp792Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TGM1
NM_000359.3 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.15
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050619185).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TGM1NM_000359.3 linkuse as main transcriptc.2376T>A p.Asp792Glu missense_variant 15/15 ENST00000206765.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TGM1ENST00000206765.11 linkuse as main transcriptc.2376T>A p.Asp792Glu missense_variant 15/151 NM_000359.3 P1P22735-1
TGM1ENST00000544573.5 linkuse as main transcriptc.1050T>A p.Asp350Glu missense_variant 9/92 P22735-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 01, 2022The c.2376T>A (p.D792E) alteration is located in exon 15 (coding exon 14) of the TGM1 gene. This alteration results from a T to A substitution at nucleotide position 2376, causing the aspartic acid (D) at amino acid position 792 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.072
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
0.014
DANN
Benign
0.54
DEOGEN2
Benign
0.19
T;.
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.041
N
M_CAP
Benign
0.028
D
MetaRNN
Benign
0.051
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.0
N;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.36
T
PROVEAN
Benign
0.22
N;N
REVEL
Benign
0.062
Sift
Benign
0.56
T;T
Sift4G
Benign
0.95
T;T
Polyphen
0.0040
B;.
Vest4
0.062
MutPred
0.14
Loss of sheet (P = 0.0817);.;
MVP
0.65
MPC
0.25
ClinPred
0.037
T
GERP RS
0.12
Varity_R
0.034
gMVP
0.31

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: chr14-24718597; API