rs456396

chr9-132687413-G-Achr9-132687413-G-Cchr9-132687413-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GTF3C4	NM_012204.4	c.2404+86G>A		intron_variant		ENST00000372146.5
GTF3C4	NR_133925.1	n.3006+86G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF3C4	ENST00000372146.5	c.2404+86G>A		intron_variant		1	NM_012204.4	P1

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

Gnomad4 AFR exome AF: 0.671

Gnomad4 AMR exome AF: 0.590

Gnomad4 ASJ exome AF: 0.457

Gnomad4 EAS exome AF: 0.647

Gnomad4 SAS exome AF: 0.421

Gnomad4 FIN exome AF: 0.591

Gnomad4 NFE exome AF: 0.514

Gnomad4 OTH exome AF: 0.535

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

Gnomad4 AFR AF: 0.638

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.363

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.453

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.473

Alfa AF: 0.395 Hom.: 19721

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

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: rs456396; hg19: chr9-135562800;