9-132687413-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_012204.4(GTF3C4):​c.2404+86G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 672,296 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 0.00034 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00034 (0 hom.)
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C4	NM_012204.4	c.2404+86G>T		intron_variant	Intron 4 of 4	ENST00000372146.5	NP_036336.2
GTF3C4	NR_133925.1	n.3006+86G>T		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>T		intron_variant	Intron 4 of 4	1	NM_012204.4	ENSP00000361219.4

Frequencies

GnomAD3 genomes AF: 0.000338 AC: 48 AN: 142030 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000597

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000583

Gnomad OTH AF: 0.000520

GnomAD4 exome AF: 0.000336 AC: 178 AN: 530266 Hom.: 0 AF XY: 0.000292 AC XY: 84 AN XY: 288042

African (AFR) AF: 0.000178 AC: 3 AN: 16828

American (AMR) AF: 0.0000749 AC: 3 AN: 40064

Ashkenazi Jewish (ASJ) AF: 0.000703 AC: 11 AN: 15654

East Asian (EAS) AF: 0.0000693 AC: 2 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: 0.000515 AC: 153 AN: 296978

Other (OTH) AF: 0.000225 AC: 6 AN: 26650

GnomAD4 genome AF: 0.000338 AC: 48 AN: 142030 Hom.: 0 Cov.: 24 AF XY: 0.000337 AC XY: 23 AN XY: 68212

African (AFR) AF: 0.000178 AC: 7 AN: 39354

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

Ashkenazi Jewish (ASJ) AF: 0.000597 AC: 2 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: 0.00 AC: 0 AN: 8944

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

European-Non Finnish (NFE) AF: 0.000583 AC: 38 AN: 65212

Other (OTH) AF: 0.000520 AC: 1 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	-0.83
CADD	Benign	0.10
DANN	Benign	0.59
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;