Variant 20-2309687-C-A 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.38C>A(p.Thr13Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,613,856 control chromosomes in the GnomAD database, including 535,774 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict 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 0.73 ( 42987 hom., cov: 32)

Exomes 𝑓: 0.82 ( 492787 hom. )

Consequence

TGM3
NM_003245.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.43

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=9.677294E-7).

BP6

Variant 20-2309687-C-A is Benign according to our data. Variant chr20-2309687-C-A is described in ClinVar as [Benign]. Clinvar id is 3060440.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.912 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.38C>A	p.Thr13Lys	missense_variant	2/13	ENST00000381458.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGM3	ENST00000381458.6 linkuse as main transcript	c.38C>A	p.Thr13Lys	missense_variant	2/13	1	NM_003245.4	P1

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111525

AN:

151970

Hom.:

42964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.845

Gnomad AMR

AF:

0.838

Gnomad ASJ

AF:

0.792

Gnomad EAS

AF:

0.934

Gnomad SAS

AF:

0.840

Gnomad FIN

AF:

0.859

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.823

Gnomad OTH

AF:

0.756

GnomAD3 exomes

AF:

0.819

AC:

205989

AN:

251430

Hom.:

85798

AF XY:

0.823

AC XY:

111783

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.462

Gnomad AMR exome

AF:

0.893

Gnomad ASJ exome

AF:

0.779

Gnomad EAS exome

AF:

0.933

Gnomad SAS exome

AF:

0.837

Gnomad FIN exome

AF:

0.863

Gnomad NFE exome

AF:

0.821

Gnomad OTH exome

AF:

0.804

GnomAD4 exome

AF:

0.818

AC:

1196237

AN:

1461768

Hom.:

492787

Cov.:

AF XY:

0.819

AC XY:

595705

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.455

Gnomad4 AMR exome

AF:

0.887

Gnomad4 ASJ exome

AF:

0.780

Gnomad4 EAS exome

AF:

0.946

Gnomad4 SAS exome

AF:

0.835

Gnomad4 FIN exome

AF:

0.859

Gnomad4 NFE exome

AF:

0.821

Gnomad4 OTH exome

AF:

0.803

GnomAD4 genome

AF:

0.734

AC:

111603

AN:

152088

Hom.:

42987

Cov.:

AF XY:

0.740

AC XY:

55046

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.471

Gnomad4 AMR

AF:

0.839

Gnomad4 ASJ

AF:

0.792

Gnomad4 EAS

AF:

0.934

Gnomad4 SAS

AF:

0.839

Gnomad4 FIN

AF:

0.859

Gnomad4 NFE

AF:

0.823

Gnomad4 OTH

AF:

0.758

Alfa

AF:

0.803

Hom.:

92748

Bravo

AF:

0.720

TwinsUK

AF:

0.821

AC:

3044

ALSPAC

AF:

0.822

AC:

3169

ESP6500AA

AF:

0.485

AC:

2137

ESP6500EA

AF:

0.821

AC:

7058

ExAC

AF:

0.810

AC:

98372

Asia WGS

AF:

0.877

AC:

3052

AN:

3478

EpiCase

AF:

0.813

EpiControl

AF:

0.806

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

Apr 16, 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

0.090

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.0080

DANN

Benign

0.44

DEOGEN2

Benign

0.16

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.10

MetaRNN

Benign

9.7e-7

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.69

MutationTaster

Benign

1.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.21

REVEL

Benign

0.17

Sift

Benign

0.69

Sift4G

Benign

0.64

Polyphen

0.73

Vest4

0.037

MPC

0.096

ClinPred

0.0052

GERP RS

-1.1

Varity_R

0.17

gMVP

0.42

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