chr14-24262037-G-C

Position:

• chr14-24262037-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000206765.11(TGM1):​c.316C>G​(p.Arg106Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,236 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TGM1 ENST00000206765.11 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24402133).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM1	NM_000359.3	c.316C>G	p.Arg106Gly	missense_variant	2/15	ENST00000206765.11	NP_000350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM1	ENST00000206765.11	c.316C>G	p.Arg106Gly	missense_variant	2/15	1	NM_000359.3	ENSP00000206765	P1
TGM1	ENST00000558074.1	c.316C>G	p.Arg106Gly	missense_variant	3/4	5		ENSP00000453840
TGM1	ENST00000544573.5	c.-29+90C>G		intron_variant		2		ENSP00000439446

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000402 AC: 1 AN: 248890 Hom.: 0 AF XY: 0.00000741 AC XY: 1 AN XY: 135012

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461236 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726934

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: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.080
FATHMM_MKL	Uncertain	0.77	D
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.55	N;.
MutationTaster	Benign	1.0	D;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.80	N;D
REVEL	Uncertain	0.44
Sift	Benign	0.24	T;D
Sift4G	Benign	0.30	T;D
Polyphen		0.92	P;.
Vest4		0.47
MutPred		0.33		Loss of MoRF binding (P = 0.0199);Loss of MoRF binding (P = 0.0199);
MVP		0.97
MPC		0.47
ClinPred		0.31	T
GERP RS		2.9
Varity_R		0.13
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs773303931; hg19: chr14-24731243;