Variant 15-43234776-G-C 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.1868C>G(p.Thr623Arg) 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 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TGM5
NM_201631.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0100

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:

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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=0.23077393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGM5	NM_201631.4 link	c.1868C>G	p.Thr623Arg	missense_variant	Exon 11 of 13	ENST00000220420.10	NP_963925.2	O43548-1B4DPS8
TGM5	NM_004245.4 link	c.1622C>G	p.Thr541Arg	missense_variant	Exon 10 of 12		NP_004236.1	O43548-2B4DPS8
TGM5	XM_011522230.3 link	c.839C>G	p.Thr280Arg	missense_variant	Exon 5 of 7		XP_011520532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TGM5	ENST00000220420.10 link	c.1868C>G	p.Thr623Arg	missense_variant	Exon 11 of 13	1	NM_201631.4	ENSP00000220420.5	O43548-1
TGM5	ENST00000349114.8 link	c.1622C>G	p.Thr541Arg	missense_variant	Exon 10 of 12	1		ENSP00000220419.8	O43548-2
TGM5	ENST00000396996.3 link	n.1344C>G		non_coding_transcript_exon_variant	Exon 4 of 6	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251482

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461850

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.35

CADD

Benign

7.8

DANN

Benign

0.95

DEOGEN2

Benign

0.027

T;T;T;.;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.75

T;T;T;T;T

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.23

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.1

.;.;M;.;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

.;.;D;.;D

REVEL

Benign

0.15

Sift

Uncertain

0.0040

.;.;D;.;D

Sift4G

Benign

0.23

T;T;T;T;T

Polyphen

0.68, 0.96

.;.;P;.;D

Vest4

0.33, 0.33

MutPred

0.50

.;.;Loss of glycosylation at T623 (P = 0.0717);.;.;

MVP

0.31

MPC

0.39

ClinPred

0.68

GERP RS

0.69

Varity_R

0.43

gMVP

0.31

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over