Variant chr8-55786265-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_024831.8(TGS1):c.367A>G(p.Lys123Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00104 in 1,473,620 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 6 hom. )

Consequence

TGS1
NM_024831.8 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.26

Variant links:

Genes affected

TGS1 (HGNC:17843): (trimethylguanosine synthase 1) Enables RNA trimethylguanosine synthase activity. Involved in 7-methylguanosine cap hypermethylation. Located in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TGS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004612088).

BP6

Variant 8-55786265-A-G is Benign according to our data. Variant chr8-55786265-A-G is described in ClinVar as [Benign]. Clinvar id is 776335.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGS1	NM_024831.8 linkuse as main transcript	c.367A>G	p.Lys123Glu	missense_variant	4/13	ENST00000260129.6	NP_079107.6	Q96RS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TGS1	ENST00000260129.6 linkuse as main transcript	c.367A>G	p.Lys123Glu	missense_variant	4/13	1	NM_024831.8	ENSP00000260129.5	Q96RS0
TGS1	ENST00000523948.5 linkuse as main transcript	n.*140A>G		non_coding_transcript_exon_variant	3/11	1		ENSP00000430467.1	E5RJW7
TGS1	ENST00000523948.5 linkuse as main transcript	n.*140A>G		3_prime_UTR_variant	3/11	1		ENSP00000430467.1	E5RJW7

Frequencies

GnomAD3 genomes

AF:

0.00367

AC:

559

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

Gnomad ASJ

AF:

0.0204

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00182

AC:

311

AN:

171212

Hom.:

AF XY:

0.00148

AC XY:

138

AN XY:

93468

show subpopulations

Gnomad AFR exome

AF:

0.0109

Gnomad AMR exome

AF:

0.00126

Gnomad ASJ exome

AF:

0.0191

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000297

Gnomad OTH exome

AF:

0.00141

GnomAD4 exome

AF:

0.000733

AC:

969

AN:

1321276

Hom.:

Cov.:

AF XY:

0.000677

AC XY:

446

AN XY:

658882

show subpopulations

Gnomad4 AFR exome

AF:

0.0103

Gnomad4 AMR exome

AF:

0.00148

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000136

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.00186

GnomAD4 genome

AF:

0.00368

AC:

560

AN:

152344

Hom.:

Cov.:

AF XY:

0.00354

AC XY:

264

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0108

Gnomad4 AMR

AF:

0.00137

Gnomad4 ASJ

AF:

0.0204

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00289

Hom.:

Bravo

AF:

0.00399

ESP6500AA

AF:

0.0113

AC:

ESP6500EA

AF:

0.000588

AC:

ExAC

AF:

0.00153

AC:

182

Asia WGS

AF:

0.000578

AC:

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.073

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0046

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-0.66

REVEL

Benign

0.11

Sift

Benign

0.039

Sift4G

Benign

0.46

Polyphen

0.65

Vest4

0.41

MVP

0.67

MPC

0.14

ClinPred

0.031

GERP RS

5.7

Varity_R

0.14

gMVP

0.15

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