rs7604809

Variant names:

• chr2-196767648-A-C
• rs7604809
• NM_012086.5:c.2386-931T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-196767648-A-C
• chr2-196767648-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_012086.5(GTF3C3):​c.2386-931T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,204 control chromosomes in the GnomAD database, including 1,092 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 0.12 (1092 hom., cov: 33)
• Consequence: GTF3C3 NM_012086.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.967
• Publications: 5 publications found

Genes affected

GTF3C3 (HGNC:4666): (general transcription factor IIIC subunit 3) The protein encoded by this gene is part of the TFIIIC2 complex, which binds to the promoters of small nuclear and cytoplasmic RNA genes in order to recruit RNA polymerase III. The TFIIIC2 complex is composed of six subunits. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

GTF3C3 Gene-Disease associations (from GenCC):

• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C3	NM_012086.5	c.2386-931T>G		intron_variant	Intron 16 of 17	ENST00000263956.8	NP_036218.1
GTF3C3	XM_005246965.5	c.1210-931T>G		intron_variant	Intron 9 of 10		XP_005247022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C3	ENST00000263956.8	c.2386-931T>G		intron_variant	Intron 16 of 17	1	NM_012086.5	ENSP00000263956.3
GTF3C3	ENST00000651042.1	n.*718-931T>G		intron_variant	Intron 17 of 18			ENSP00000499170.1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 18002 AN: 152086 Hom.: 1091 Cov.: 33

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.0980

Gnomad EAS AF: 0.0239

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.119

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

GnomAD4 genome AF: 0.118 AC: 18019 AN: 152204 Hom.: 1092 Cov.: 33 AF XY: 0.115 AC XY: 8577 AN XY: 74440

African (AFR) AF: 0.114 AC: 4725 AN: 41516

American (AMR) AF: 0.0858 AC: 1312 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0980 AC: 340 AN: 3468

East Asian (EAS) AF: 0.0237 AC: 123 AN: 5186

South Asian (SAS) AF: 0.134 AC: 646 AN: 4824

European-Finnish (FIN) AF: 0.0922 AC: 977 AN: 10602

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9407 AN: 67994

Other (OTH) AF: 0.118 AC: 249 AN: 2112

Alfa AF: 0.119 Hom.: 696

Bravo AF: 0.115

Asia WGS AF: 0.0930 AC: 323 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.46
PhyloP100		0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7604809; hg19: chr2-197632372;