chr9-132687413-G-A

Variant names:

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

Variant summary

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

The NM_012204.4(GTF3C4):​c.2404+86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 672,278 control chromosomes in the GnomAD database, including 85,954 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 0.51 (17995 hom., cov: 24)
  • Exomes 𝑓: 0.53 (67959 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.506 AC: 71814 AN: 141998 Hom.: 17967 Cov.: 24

Gnomad AFR AF: 0.638

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.363

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.482

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.526 AC: 278834 AN: 530166 Hom.: 67959 AF XY: 0.516 AC XY: 148457 AN XY: 287972

African (AFR) AF: 0.671 AC: 11283 AN: 16826

American (AMR) AF: 0.590 AC: 23616 AN: 40054

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 7151 AN: 15650

East Asian (EAS) AF: 0.647 AC: 18676 AN: 28854

South Asian (SAS) AF: 0.421 AC: 26604 AN: 63212

European-Finnish (FIN) AF: 0.591 AC: 23577 AN: 39922

Middle Eastern (MID) AF: 0.463 AC: 961 AN: 2074

European-Non Finnish (NFE) AF: 0.514 AC: 152696 AN: 296924

Other (OTH) AF: 0.535 AC: 14270 AN: 26650

GnomAD4 genome AF: 0.506 AC: 71896 AN: 142112 Hom.: 17995 Cov.: 24 AF XY: 0.518 AC XY: 35362 AN XY: 68302

African (AFR) AF: 0.638 AC: 25186 AN: 39452

American (AMR) AF: 0.564 AC: 7471 AN: 13254

Ashkenazi Jewish (ASJ) AF: 0.363 AC: 1214 AN: 3348

East Asian (EAS) AF: 0.614 AC: 2896 AN: 4716

South Asian (SAS) AF: 0.453 AC: 1907 AN: 4206

European-Finnish (FIN) AF: 0.602 AC: 5379 AN: 8938

Middle Eastern (MID) AF: 0.476 AC: 98 AN: 206

European-Non Finnish (NFE) AF: 0.408 AC: 26594 AN: 65200

Other (OTH) AF: 0.473 AC: 916 AN: 1936

Alfa AF: 0.417 Hom.: 37682

Bravo AF: 0.485

Asia WGS AF: 0.481 AC: 1671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.55
PhyloP100		-0.71
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: rs456396; hg19: chr9-135562800;