rs761541189

Variant names:

• chr6-110958792-G-A
• NM_138408.4:c.23G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-110958792-G-A
• chr6-110958792-G-C
• chr6-110958792-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_138408.4(GTF3C6):​c.23G>A​(p.Arg8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,398,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: GTF3C6 NM_138408.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823

Genes affected

GTF3C6 (HGNC:20872): (general transcription factor IIIC subunit 6) RNA polymerases are unable to initiate RNA synthesis in the absence of additional proteins called general transcription factors (GTFs). GTFs assemble in a complex on the DNA promoter and recruit the RNA polymerase. GTF3C family proteins (e.g., GTF3C1, MIM 603246) are essential for RNA polymerase III to make a number of small nuclear and cytoplasmic RNAs, including 5S RNA (MIM 180420), tRNA, and adenovirus-associated (VA) RNA of both cellular and viral origin.[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0685648).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C6	NM_138408.4	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 6	ENST00000329970.8	NP_612417.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C6	ENST00000329970.8	c.23G>A	p.Arg8Gln	missense_variant	Exon 1 of 6	1	NM_138408.4	ENSP00000357863.4
GTF3C6	ENST00000480191.1	n.-136G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398734 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689896

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.040	N
REVEL	Benign	0.039
Sift	Benign	0.35	T
Sift4G	Benign	0.55	T
Polyphen		0.87	P
Vest4		0.079
MutPred		0.083		Gain of relative solvent accessibility (P = 0.09);
MVP		0.014
MPC		0.25
ClinPred		0.13	T
GERP RS		-0.055
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.034
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-111279995;