Genetic Variant NM_024831.8:c.31G>A (chr8-55773649-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024831.8(TGS1):c.31G>A(p.Glu11Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000206 in 1,458,958 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E11Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TGS1
NM_024831.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.14

Publications

3 publications found

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:

TMEM68 (HGNC:26510): (transmembrane protein 68) Predicted to enable acyltransferase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM68 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024831.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TGS1	NM_024831.8	MANE Select	c.31G>A	p.Glu11Lys	missense	Exon 1 of 13	NP_079107.6
TGS1	NM_001363184.2		c.-184G>A		5_prime_UTR	Exon 1 of 12	NP_001350113.1
TGS1	NM_001317902.2		c.-184G>A		5_prime_UTR	Exon 1 of 11	NP_001304831.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TGS1	ENST00000260129.6	TSL:1 MANE Select	c.31G>A	p.Glu11Lys	missense	Exon 1 of 13	ENSP00000260129.5	Q96RS0
TGS1	ENST00000523948.5	TSL:1	n.31G>A		non_coding_transcript_exon	Exon 1 of 11	ENSP00000430467.1	E5RJW7
TGS1	ENST00000938743.1		c.31G>A	p.Glu11Lys	missense	Exon 1 of 13	ENSP00000608802.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000807

AC:

AN:

247720

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458958

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725732

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33358

American (AMR)

AF:

0.00

AC:

AN:

44240

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39366

South Asian (SAS)

AF:

0.00

AC:

AN:

85632

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53330

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110934

Other (OTH)

AF:

0.0000166

AC:

AN:

60286

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Uncertain

-0.050

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.81

M_CAP

Benign

0.0067

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PhyloP100

4.1

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.0

REVEL

Benign

0.17

Sift

Benign

0.10

Sift4G

Benign

0.14

Polyphen

0.78

Vest4

0.60

MutPred

0.62

Gain of MoRF binding (P = 0.0045)

MVP

0.53

MPC

0.030

ClinPred

0.81

GERP RS

5.0

PromoterAI

-0.14

Neutral

(source)

Varity_R

0.34

gMVP

0.52

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over