Variant 3-44901672-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP5BS1_SupportingBS2_Supporting

The NM_003241.4(TGM4):c.806G>A(p.Trp269Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00785 in 1,614,152 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0079 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0078 ( 98 hom. )

Consequence

TGM4
NM_003241.4 stop_gained

Scores

Clinical Significance

Likely pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 5.43

Variant links:

Genes affected

TGM4 (HGNC:11780): (transglutaminase 4) Predicted to enable protein-glutamine gamma-glutamyltransferase activity. Predicted to be involved in peptide cross-linking. Predicted to act upstream of or within mating plug formation. Located in Golgi apparatus and collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

TGM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PP5

Variant 3-44901672-G-A is Pathogenic according to our data. Variant chr3-44901672-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 1184858.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00785 (11475/1461816) while in subpopulation MID AF= 0.0359 (207/5768). AF 95% confidence interval is 0.0319. There are 98 homozygotes in gnomad4_exome. There are 6052 alleles in male gnomad4_exome subpopulation. Median coverage is 64. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 12 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM4	NM_003241.4 linkuse as main transcript	c.806G>A	p.Trp269Ter	stop_gained	7/14	ENST00000296125.9	NP_003232.2
TGM4	XM_011534042.3 linkuse as main transcript	c.941G>A	p.Trp314Ter	stop_gained	8/15		XP_011532344.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGM4	ENST00000296125.9 linkuse as main transcript	c.806G>A	p.Trp269Ter	stop_gained	7/14	1	NM_003241.4	ENSP00000296125	P2
TGM4	ENST00000705784.1 linkuse as main transcript	c.941G>A	p.Trp314Ter	stop_gained	8/15			ENSP00000516167	A2

Frequencies

GnomAD3 genomes

AF:

0.00790

AC:

1203

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.0647

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0106

Gnomad FIN

AF:

0.0119

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00874

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00902

AC:

2266

AN:

251248

Hom.:

AF XY:

0.00990

AC XY:

1345

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00746

Gnomad ASJ exome

AF:

0.0206

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0137

Gnomad FIN exome

AF:

0.0116

Gnomad NFE exome

AF:

0.00920

Gnomad OTH exome

AF:

0.0114

GnomAD4 exome

AF:

0.00785

AC:

11475

AN:

1461816

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

6052

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.00164

Gnomad4 AMR exome

AF:

0.00724

Gnomad4 ASJ exome

AF:

0.0216

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0148

Gnomad4 FIN exome

AF:

0.0114

Gnomad4 NFE exome

AF:

0.00704

Gnomad4 OTH exome

AF:

0.00997

GnomAD4 genome

AF:

0.00790

AC:

1203

AN:

152336

Hom.:

Cov.:

AF XY:

0.00839

AC XY:

625

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.0119

Gnomad4 NFE

AF:

0.00873

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00888

Hom.:

Bravo

AF:

0.00799

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00834

AC:

1013

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0126

EpiControl

AF:

0.0132

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Essential tremor

Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.61

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Uncertain

0.27

Eigen_PC

Benign

-0.055

FATHMM_MKL

Uncertain

0.95

MutationTaster

Benign

1.0

Vest4

0.055

GERP RS

1.9

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.21

Position offset: 26

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