14-24249358-A-T

Variant names:

• chr14-24249358-A-T
• NM_000359.3:c.2409T>A

Variant summary

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

The NM_000359.3(TGM1):​c.2409T>A​(p.Ser803Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,792 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 31)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: TGM1 NM_000359.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.477

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=0.12751475).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM1	NM_000359.3	c.2409T>A	p.Ser803Arg	missense_variant	Exon 15 of 15	ENST00000206765.11	NP_000350.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGM1	ENST00000206765.11	c.2409T>A	p.Ser803Arg	missense_variant	Exon 15 of 15	1	NM_000359.3	ENSP00000206765.6
TGM1	ENST00000544573.5	c.1083T>A	p.Ser361Arg	missense_variant	Exon 9 of 9	2		ENSP00000439446.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000123 AC: 18 AN: 1461792 Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7 AN XY: 727176

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: 0.0000162

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	8.5
DANN	Benign	0.97
DEOGEN2	Benign	0.24	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.051	N
M_CAP	Benign	0.056	D
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	1.4	L;.
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.25
Sift	Uncertain	0.0040	D;D
Sift4G	Uncertain	0.047	D;T
Polyphen		0.079	B;.
Vest4		0.37
MutPred		0.11		Loss of glycosylation at S803 (P = 0.017);.;
MVP		0.85
MPC		0.32
ClinPred		0.15	T
GERP RS		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.11
gMVP		0.56

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: chr14-24718564;