9-132687413-G-C

Variant names:

• chr9-132687413-G-C
• rs456396
• NM_012204.4:c.2404+86G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_012204.4(GTF3C4):​c.2404+86G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000704 in 142,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000070 (0 hom., cov: 24)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF3C4 NM_012204.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.713
• Publications: 9 publications found

Genes affected

GTF3C4 (HGNC:4667): (general transcription factor IIIC subunit 4) Predicted to enable enzyme activator activity. Predicted to contribute to DNA binding activity. Predicted to be involved in 5S class rRNA transcription by RNA polymerase III and tRNA transcription by RNA polymerase III. Located in mitochondrion and nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C4	NM_012204.4	c.2404+86G>C		intron_variant	Intron 4 of 4	ENST00000372146.5	NP_036336.2
GTF3C4	NR_133925.1	n.3006+86G>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C4	ENST00000372146.5	c.2404+86G>C		intron_variant	Intron 4 of 4	1	NM_012204.4	ENSP00000361219.4

Frequencies

GnomAD3 genomes AF: 0.00000704 AC: 1 AN: 142028 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 530296 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 288050

African (AFR) AF: 0.00 AC: 0 AN: 16828

American (AMR) AF: 0.00 AC: 0 AN: 40064

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15656

East Asian (EAS) AF: 0.00 AC: 0 AN: 28856

South Asian (SAS) AF: 0.00 AC: 0 AN: 63224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2076

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 297006

Other (OTH) AF: 0.00 AC: 0 AN: 26650

GnomAD4 genome AF: 0.00000704 AC: 1 AN: 142028 Hom.: 0 Cov.: 24 AF XY: 0.0000147 AC XY: 1 AN XY: 68210

African (AFR) AF: 0.00 AC: 0 AN: 39352

American (AMR) AF: 0.00 AC: 0 AN: 13238

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3348

East Asian (EAS) AF: 0.00 AC: 0 AN: 4726

South Asian (SAS) AF: 0.00 AC: 0 AN: 4210

European-Finnish (FIN) AF: 0.000112 AC: 1 AN: 8944

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65212

Other (OTH) AF: 0.00 AC: 0 AN: 1924

Alfa AF: 0.00 Hom.: 37682

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.11
DANN	Benign	0.48
PhyloP100		-0.71

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: rs456396; hg19: chr9-135562800;