chr14-24249347-TCTC-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_000359.3(TGM1):c.2417_2419del(p.Gly806del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Consequence
TGM1
NM_000359.3 inframe_deletion
NM_000359.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.19
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 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Nonframeshift variant in NON repetitive region in NM_000359.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| TGM1 | NM_000359.3 | c.2417_2419del | p.Gly806del | inframe_deletion | 15/15 | ENST00000206765.11 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TGM1 | ENST00000206765.11 | c.2417_2419del | p.Gly806del | inframe_deletion | 15/15 | 1 | NM_000359.3 | P1 | |
| TGM1 | ENST00000544573.5 | c.1091_1093del | p.Gly364del | inframe_deletion | 9/9 | 2 |
Frequencies
GnomAD3 genomes 0.0000132 AC: 2AN: 152010Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
2
AN:
152010
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome 0.0000132 AC: 2AN: 152010Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74252
GnomAD4 genome
AF:
AC:
2
AN:
152010
Hom.:
Cov.:
31
AF XY:
AC XY:
1
AN XY:
74252
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive congenital ichthyosis 1 Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 26, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
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