rs6760828

Positions:

• chr2-27356364-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359541.6(GTF3C2):​c.-302A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 318,462 control chromosomes in the GnomAD database, including 31,529 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 0.46 (17709 hom., cov: 32)
  • Exomes 𝑓: 0.39 (13820 hom.)
• Consequence: GTF3C2 ENST00000359541.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.511

Genes affected

GTF3C2 (HGNC:4665): (general transcription factor IIIC subunit 2) Contributes to DNA binding activity. Involved in transcription by RNA polymerase III. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

GTF3C2-AS2 (HGNC:55699): (GTF3C2 antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF3C2	NM_001035521.3	c.-25+375A>G		intron_variant		ENST00000264720.8	NP_001030598.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF3C2	ENST00000264720.8	c.-25+375A>G		intron_variant		1	NM_001035521.3	ENSP00000264720	P1

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70409 AN: 151932 Hom.: 17652 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.406

GnomAD4 exome AF: 0.393 AC: 65388 AN: 166414 Hom.: 13820 Cov.: 0 AF XY: 0.390 AC XY: 35899 AN XY: 92072

Gnomad4 AFR exome AF: 0.647

Gnomad4 AMR exome AF: 0.514

Gnomad4 ASJ exome AF: 0.343

Gnomad4 EAS exome AF: 0.146

Gnomad4 SAS exome AF: 0.398

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.384

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.464 AC: 70539 AN: 152048 Hom.: 17709 Cov.: 32 AF XY: 0.463 AC XY: 34409 AN XY: 74324

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.150

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.410

Alfa AF: 0.422 Hom.: 3402

Bravo AF: 0.473

Asia WGS AF: 0.348 AC: 1209 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.1
DANN	Benign	0.68

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: rs6760828; hg19: chr2-27579231;