rs7604809

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GTF3C3	NM_012086.5	c.2386-931T>G		intron_variant		ENST00000263956.8
GTF3C3	XM_005246965.5	c.1210-931T>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF3C3	ENST00000263956.8	c.2386-931T>G		intron_variant		1	NM_012086.5	P1
GTF3C3	ENST00000651042.1	c.*718-931T>G		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0858

Gnomad4 ASJ AF: 0.0980

Gnomad4 EAS AF: 0.0237

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.118

Alfa AF: 0.118 Hom.: 624

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs7604809; hg19: chr2-197632372;