Variant 20-2311076-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_003245.4(TGM3):c.487A>C(p.Ile163Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 1,614,048 control chromosomes in the GnomAD database, including 5,324 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.10 ( 2829 hom., cov: 32)

Exomes 𝑓: 0.011 ( 2495 hom. )

Consequence

TGM3
NM_003245.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.22

Variant links:

Genes affected

TGM3 (HGNC:11779): (transglutaminase 3) Transglutaminases are enzymes that catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds. While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent. The protein encoded by this gene consists of two polypeptide chains activated from a single precursor protein by proteolysis. The encoded protein is involved the later stages of cell envelope formation in the epidermis and hair follicle. [provided by RefSeq, Jul 2008]

TGM3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028204918).

BP6

Variant 20-2311076-A-C is Benign according to our data. Variant chr20-2311076-A-C is described in ClinVar as [Benign]. Clinvar id is 3060634.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr20-2311076-A-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGM3	NM_003245.4 linkuse as main transcript	c.487A>C	p.Ile163Leu	missense_variant	4/13	ENST00000381458.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM3	ENST00000381458.6 linkuse as main transcript	c.487A>C	p.Ile163Leu	missense_variant	4/13	1	NM_003245.4	P1

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15925

AN:

152090

Hom.:

2823

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0458

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.0793

GnomAD3 exomes

AF:

0.0272

AC:

6831

AN:

251408

Hom.:

1086

AF XY:

0.0194

AC XY:

2638

AN XY:

135874

show subpopulations

Gnomad AFR exome

AF:

0.367

Gnomad AMR exome

AF:

0.0179

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00107

Gnomad OTH exome

AF:

0.0171

GnomAD4 exome

AF:

0.0109

AC:

15931

AN:

1461840

Hom.:

2495

Cov.:

AF XY:

0.00943

AC XY:

6858

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.375

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000678

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.105

AC:

15960

AN:

152208

Hom.:

2829

Cov.:

AF XY:

0.100

AC XY:

7473

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.362

Gnomad4 AMR

AF:

0.0457

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00121

Gnomad4 OTH

AF:

0.0785

Alfa

AF:

0.0158

Hom.:

632

Bravo

AF:

0.121

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.341

AC:

1503

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.0340

AC:

4127

Asia WGS

AF:

0.0220

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

TGM3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0028

MetaSVM

Benign

-1.3

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

0.000097

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.41

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.020

Polyphen

0.91

Vest4

0.11

MPC

0.085

ClinPred

0.086

GERP RS

5.7

Varity_R

0.39

gMVP

0.53

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