Variant 8-55773673-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024831.8(TGS1):c.55C>G(p.Arg19Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,610,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

TGS1
NM_024831.8 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.92

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10350481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGS1	NM_024831.8 linkuse as main transcript	c.55C>G	p.Arg19Gly	missense_variant	1/13	ENST00000260129.6	NP_079107.6	Q96RS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TGS1	ENST00000260129.6 linkuse as main transcript	c.55C>G	p.Arg19Gly	missense_variant	1/13	1	NM_024831.8	ENSP00000260129.5		Q96RS0
TGS1	ENST00000523948.5 linkuse as main transcript	n.55C>G		non_coding_transcript_exon_variant	1/11	1		ENSP00000430467.1		E5RJW7

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000243

AC:

AN:

247414

Hom.:

AF XY:

0.0000149

AC XY:

AN XY:

133830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000960

AC:

AN:

1458248

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

725384

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000272

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000982

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000110

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2023

The c.55C>G (p.R19G) alteration is located in exon 1 (coding exon 1) of the TGS1 gene. This alteration results from a C to G substitution at nucleotide position 55, causing the arginine (R) at amino acid position 19 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.025

Eigen

Benign

-0.080

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.56

M_CAP

Benign

0.0030

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.30

REVEL

Benign

0.047

Sift

Benign

0.047

Sift4G

Benign

0.26

Polyphen

0.21

Vest4

0.13

MutPred

0.39

Gain of loop (P = 0.0079);

MVP

0.55

MPC

0.023

ClinPred

0.32

GERP RS

5.0

Varity_R

0.23

gMVP

0.38

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