rs12678930

chr8-55813718-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024831.8(TGS1):c.2439+600A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 151,806 control chromosomes in the GnomAD database, including 17,021 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17021 hom., cov: 32)
• Consequence: TGS1 NM_024831.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TGS1	NM_024831.8	c.2439+600A>G		intron_variant		ENST00000260129.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TGS1	ENST00000260129.6	c.2439+600A>G		intron_variant		1	NM_024831.8	P1
TGS1	ENST00000523948.5	c.*1980+600A>G		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.470 AC: 71270 AN: 151688 Hom.: 17017 Cov.: 32

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.588

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.501

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.470 AC: 71280 AN: 151806 Hom.: 17021 Cov.: 32 AF XY: 0.473 AC XY: 35121 AN XY: 74206

Gnomad4 AFR AF: 0.392

Gnomad4 AMR AF: 0.543

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.587

Gnomad4 SAS AF: 0.539

Gnomad4 FIN AF: 0.501

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.494

Alfa AF: 0.468 Hom.: 2109

Bravo AF: 0.471

Asia WGS AF: 0.541 AC: 1877 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.13
Dann	Benign	0.45

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

Other links and lift over

dbSNP: rs12678930; hg19: chr8-56726277;