rs12678930

Variant names:

• chr8-55813718-A-G
• rs12678930
• NM_024831.8:c.2439+600A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGS1	NM_024831.8	MANE Select	c.2439+600A>G		intron	N/A	NP_079107.6
	TGS1	NM_001363184.2		c.2160+600A>G		intron	N/A	NP_001350113.1
	TGS1	NM_001317902.2		c.1928+600A>G		intron	N/A	NP_001304831.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TGS1	ENST00000260129.6	TSL:1 MANE Select	c.2439+600A>G		intron	N/A	ENSP00000260129.5	Q96RS0
	TGS1	ENST00000523948.5	TSL:1	n.*1980+600A>G		intron	N/A	ENSP00000430467.1	E5RJW7
	TGS1	ENST00000938743.1		c.2436+600A>G		intron	N/A	ENSP00000608802.1

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

African (AFR) AF: 0.392 AC: 16205 AN: 41366

American (AMR) AF: 0.543 AC: 8289 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.502 AC: 1737 AN: 3458

East Asian (EAS) AF: 0.587 AC: 3028 AN: 5158

South Asian (SAS) AF: 0.539 AC: 2597 AN: 4816

European-Finnish (FIN) AF: 0.501 AC: 5258 AN: 10494

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32748 AN: 67940

Other (OTH) AF: 0.494 AC: 1042 AN: 2110

Alfa AF: 0.465 Hom.: 2173

Bravo AF: 0.471

Asia WGS AF: 0.541 AC: 1877 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.13
DANN	Benign	0.45
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12678930; hg19: chr8-56726277;