Variant 8-55786376-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000260129.6(TGS1):c.478A>G(p.Ile160Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00507 in 1,613,694 control chromosomes in the GnomAD database, including 153 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.018 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 85 hom. )

Consequence

TGS1
ENST00000260129.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.236

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0018075705).

BP6

Variant 8-55786376-A-G is Benign according to our data. Variant chr8-55786376-A-G is described in ClinVar as [Benign]. Clinvar id is 785250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGS1	NM_024831.8 linkuse as main transcript	c.478A>G	p.Ile160Val	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.478A>G	p.Ile160Val	missense_variant	4/13	1	NM_024831.8	ENSP00000260129.5	Q96RS0
TGS1	ENST00000523948.5 linkuse as main transcript	n.*251A>G		non_coding_transcript_exon_variant	3/11	1		ENSP00000430467.1	E5RJW7
TGS1	ENST00000523948.5 linkuse as main transcript	n.*251A>G		3_prime_UTR_variant	3/11	1		ENSP00000430467.1	E5RJW7

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2706

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00827

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000897

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00852

AC:

2134

AN:

250414

Hom.:

AF XY:

0.00721

AC XY:

976

AN XY:

135322

show subpopulations

Gnomad AFR exome

AF:

0.0508

Gnomad AMR exome

AF:

0.00425

Gnomad ASJ exome

AF:

0.00129

Gnomad EAS exome

AF:

0.0130

Gnomad SAS exome

AF:

0.00158

Gnomad FIN exome

AF:

0.0309

Gnomad NFE exome

AF:

0.00137

Gnomad OTH exome

AF:

0.00671

GnomAD4 exome

AF:

0.00375

AC:

5478

AN:

1461364

Hom.:

Cov.:

AF XY:

0.00351

AC XY:

2555

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.0542

Gnomad4 AMR exome

AF:

0.00459

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.0189

Gnomad4 SAS exome

AF:

0.00159

Gnomad4 FIN exome

AF:

0.0290

Gnomad4 NFE exome

AF:

0.000495

Gnomad4 OTH exome

AF:

0.00689

GnomAD4 genome

AF:

0.0178

AC:

2710

AN:

152330

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1353

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0507

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00829

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0295

Gnomad4 NFE

AF:

0.000897

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00266

Hom.:

Bravo

AF:

0.0179

ESP6500AA

AF:

0.0488

AC:

215

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.00922

AC:

1119

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000474

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	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.029

DANN

Benign

0.25

DEOGEN2

Benign

0.011

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0043

LIST_S2

Benign

0.26

MetaRNN

Benign

0.0018

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-2.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

0.11

REVEL

Benign

0.044

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.013

MVP

0.19

MPC

0.020

ClinPred

0.000011

GERP RS

-1.7

Varity_R

0.017

gMVP

0.058

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