Variant 15-43234825-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_201631.4(TGM5):c.1819G>A(p.Glu607Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TGM5
NM_201631.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.565

Variant links:

Genes affected

TGM5 (HGNC:11781): (transglutaminase 5) This gene encodes a member of the transglutaminase family. The encoded protein catalyzes formation of protein cross-links between glutamine and lysine residues, often resulting in stabilization of protein assemblies. This reaction is calcium dependent. Mutations in this gene have been associated with acral peeling skin syndrome. [provided by RefSeq, Oct 2009]

TGM5 links:

TGM5 (HGNC:):

TGM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.09165195).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM5	NM_201631.4 linkuse as main transcript	c.1819G>A	p.Glu607Lys	missense_variant	11/13	ENST00000220420.10	NP_963925.2	O43548-1B4DPS8
TGM5	NM_004245.4 linkuse as main transcript	c.1573G>A	p.Glu525Lys	missense_variant	10/12		NP_004236.1	O43548-2B4DPS8
TGM5	XM_011522230.3 linkuse as main transcript	c.790G>A	p.Glu264Lys	missense_variant	5/7		XP_011520532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TGM5	ENST00000220420.10 linkuse as main transcript	c.1819G>A	p.Glu607Lys	missense_variant	11/13	1	NM_201631.4	ENSP00000220420.5	O43548-1
TGM5	ENST00000349114.8 linkuse as main transcript	c.1573G>A	p.Glu525Lys	missense_variant	10/12	1		ENSP00000220419.8	O43548-2
TGM5	ENST00000396996.3 linkuse as main transcript	n.1295G>A		non_coding_transcript_exon_variant	4/6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251494

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135920

show subpopulations

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727244

show subpopulations

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Jul 17, 2023

The c.1819G>A (p.E607K) alteration is located in exon 11 (coding exon 11) of the TGM5 gene. This alteration results from a G to A substitution at nucleotide position 1819, causing the glutamic acid (E) at amino acid position 607 to be replaced by a lysine (K). 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

0.074

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.028

T;T;T;.;.

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.76

T;T;T;T;T

M_CAP

Benign

0.040

MetaRNN

Benign

0.092

T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.1

.;.;M;.;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.5

.;.;N;.;N

REVEL

Benign

0.042

Sift

Benign

0.047

.;.;D;.;T

Sift4G

Benign

0.16

T;T;T;T;T

Polyphen

0.0040, 0.20

.;.;B;.;B

Vest4

0.27, 0.28

MutPred

0.45

.;.;Gain of methylation at E607 (P = 0.0129);.;.;

MVP

0.24

MPC

0.17

ClinPred

0.24

GERP RS

1.9

Varity_R

0.10

gMVP

0.44

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over