Genetic Variant TGS1:p.Asp150Asn (chr8-55786346-G-A) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_024831.8(TGS1):c.448G>A(p.Asp150Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00706 in 1,612,404 control chromosomes in the GnomAD database, including 62 homozygotes. 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.0049 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0073 ( 57 hom. )

Consequence

TGS1
NM_024831.8 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.06

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=0.0028980374).

BP6

Variant 8-55786346-G-A is Benign according to our data. Variant chr8-55786346-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 782749.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGS1	NM_024831.8 link	c.448G>A	p.Asp150Asn	missense_variant	Exon 4 of 13	ENST00000260129.6	NP_079107.6	Q96RS0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TGS1	ENST00000260129.6 link	c.448G>A	p.Asp150Asn	missense_variant	Exon 4 of 13	1	NM_024831.8	ENSP00000260129.5	Q96RS0
TGS1	ENST00000523948.5 link	n.*221G>A		non_coding_transcript_exon_variant	Exon 3 of 11	1		ENSP00000430467.1	E5RJW7
TGS1	ENST00000523948.5 link	n.*221G>A		3_prime_UTR_variant	Exon 3 of 11	1		ENSP00000430467.1	E5RJW7

Frequencies

GnomAD3 genomes

AF:

0.00487

AC:

741

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00892

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00525

AC:

1312

AN:

249990

Hom.:

AF XY:

0.00536

AC XY:

725

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.000804

Gnomad AMR exome

AF:

0.00140

Gnomad ASJ exome

AF:

0.00557

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00245

Gnomad FIN exome

AF:

0.00208

Gnomad NFE exome

AF:

0.00913

Gnomad OTH exome

AF:

0.00707

GnomAD4 exome

AF:

0.00729

AC:

10640

AN:

1460142

Hom.:

Cov.:

AF XY:

0.00727

AC XY:

5281

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.00123

Gnomad4 AMR exome

AF:

0.00153

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00273

Gnomad4 FIN exome

AF:

0.00219

Gnomad4 NFE exome

AF:

0.00862

Gnomad4 OTH exome

AF:

0.00699

GnomAD4 genome

AF:

0.00486

AC:

740

AN:

152262

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

320

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00128

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00189

Gnomad4 NFE

AF:

0.00893

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00790

Hom.:

Bravo

AF:

0.00494

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00568

AC:

689

Asia WGS

AF:

0.000578

AC:

AN:

3476

EpiCase

AF:

0.00971

EpiControl

AF:

0.00794

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 02, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TGS1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.032

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.79

M_CAP

Benign

0.012

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.88

REVEL

Benign

0.085

Sift

Benign

0.24

Sift4G

Benign

0.28

Polyphen

0.15

Vest4

0.10

MVP

0.50

MPC

0.055

ClinPred

0.0065

GERP RS

4.9

Varity_R

0.036

gMVP

0.11

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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