NM_024831.8:c.196G>A

Variant names:

• chr8-55785748-G-A
• rs148882143
• NM_024831.8:c.196G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024831.8(TGS1):​c.196G>A​(p.Gly66Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. G66R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TGS1 NM_024831.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0511418).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TGS1	NM_024831.8	c.196G>A	p.Gly66Ser	missense_variant	Exon 3 of 13	ENST00000260129.6	NP_079107.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TGS1	ENST00000260129.6	c.196G>A	p.Gly66Ser	missense_variant	Exon 3 of 13	1	NM_024831.8	ENSP00000260129.5
TGS1	ENST00000523948.5	n.131G>A		non_coding_transcript_exon_variant	Exon 2 of 11	1		ENSP00000430467.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.3
DANN	Benign	0.90
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.22	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.034
Sift	Benign	0.35	T
Sift4G	Benign	0.58	T
Polyphen		0.0010	B
Vest4		0.059
MutPred		0.077		Gain of glycosylation at G66 (P = 0.0106);
MVP		0.44
MPC		0.021
ClinPred		0.080	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.038
gMVP		0.098

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

LitVar

Other links and lift over

dbSNP: rs148882143; hg19: chr8-56698307;