15-43279148-A-T

Position:

• chr15-43279148-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_052955.3(TGM7):​c.1808T>A​(p.Ile603Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGM7 NM_052955.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.54

Genes affected

TGM7 (HGNC:30790): (transglutaminase 7) Transglutaminases (TGM; EC 2.3.2.13) are a family of structurally and functionally related enzymes that stabilize protein assemblies through the formation of gamma-glutamyl-epsilon lysine crosslinks. For additional background information on transglutaminases, see TGM1 (MIM 190195).[supplied by OMIM, Jul 2002]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.876

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM7	NM_052955.3	c.1808T>A	p.Ile603Asn	missense_variant	11/13	ENST00000452443.3	NP_443187.1
TGM7	XM_017021903.1	c.1811T>A	p.Ile604Asn	missense_variant	11/13		XP_016877392.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM7	ENST00000452443.3	c.1808T>A	p.Ile603Asn	missense_variant	11/13	1	NM_052955.3	ENSP00000389466	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 10, 2024

The c.1808T>A (p.I603N) alteration is located in exon 11 (coding exon 11) of the TGM7 gene. This alteration results from a T to A substitution at nucleotide position 1808, causing the isoleucine (I) at amino acid position 603 to be replaced by an asparagine (N). 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	Uncertain	0.51
BayesDel_addAF	Benign	-0.054	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.36	T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.88	D
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.4	M
MutationTaster	Benign	0.92	N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.96	P
Vest4		0.70
MutPred		0.75		Loss of stability (P = 0.0254);
MVP		0.67
MPC		0.49
ClinPred		0.99	D
GERP RS		5.1
Varity_R		0.86
gMVP		0.82

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: chr15-43571346;