Variant 8-55785806-G-A 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_001363184.2(TGS1):c.-26G>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00627 in 1,613,986 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0065 ( 34 hom. )

Consequence

TGS1
NM_001363184.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0660

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=0.0055455863).

BP6

Variant 8-55785806-G-A is Benign according to our data. Variant chr8-55785806-G-A is described in ClinVar as [Benign]. Clinvar id is 776600.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGS1	NM_024831.8 linkuse as main transcript	c.254G>A	p.Ser85Asn	missense_variant	3/13	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.254G>A	p.Ser85Asn	missense_variant	3/13	1	NM_024831.8	ENSP00000260129.5	Q96RS0
TGS1	ENST00000523948.5 linkuse as main transcript	n.*27G>A		non_coding_transcript_exon_variant	2/11	1		ENSP00000430467.1	E5RJW7
TGS1	ENST00000523948.5 linkuse as main transcript	n.*27G>A		3_prime_UTR_variant	2/11	1		ENSP00000430467.1	E5RJW7

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

606

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00311

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00656

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00437

AC:

1097

AN:

251176

Hom.:

AF XY:

0.00439

AC XY:

596

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.00883

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.00240

Gnomad NFE exome

AF:

0.00700

Gnomad OTH exome

AF:

0.00375

GnomAD4 exome

AF:

0.00651

AC:

9512

AN:

1461664

Hom.:

Cov.:

AF XY:

0.00630

AC XY:

4584

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00788

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00123

Gnomad4 FIN exome

AF:

0.00285

Gnomad4 NFE exome

AF:

0.00771

Gnomad4 OTH exome

AF:

0.00525

GnomAD4 genome

AF:

0.00398

AC:

606

AN:

152322

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

277

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00806

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00311

Gnomad4 NFE

AF:

0.00656

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00665

Hom.:

Bravo

AF:

0.00407

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00640

AC:

ExAC

AF:

0.00414

AC:

503

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00704

EpiControl

AF:

0.00706

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	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 02, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.37

DEOGEN2

Benign

0.027

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.79

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.32

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0055

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.32

PROVEAN

Benign

0.30

REVEL

Benign

0.047

Sift

Benign

0.47

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.12

MVP

0.32

MPC

0.021

ClinPred

0.0017

GERP RS

1.6

Varity_R

0.028

gMVP

0.091

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