rs1049817

chr2-27328100-A-Gchr2-27328100-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001035521.3(GTF3C2):c.2346T>C(p.Pro782=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 1,609,112 control chromosomes in the GnomAD database, including 139,582 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 0.47 (18591 hom., cov: 32)
  • Exomes 𝑓: 0.40 (120991 hom.)
• Consequence: GTF3C2 NM_001035521.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.246

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.246 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF3C2	NM_001035521.3	c.2346T>C	p.Pro782=	synonymous_variant	17/19	ENST00000264720.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF3C2	ENST00000264720.8	c.2346T>C	p.Pro782=	synonymous_variant	17/19	1	NM_001035521.3	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71710 AN: 151934 Hom.: 18532 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.416

GnomAD3 exomes AF: 0.419 AC: 104001 AN: 248488 Hom.: 23762 AF XY: 0.407 AC XY: 54753 AN XY: 134464

Gnomad AFR exome AF: 0.693

Gnomad AMR exome AF: 0.558

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.152

Gnomad SAS exome AF: 0.405

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.387

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.400 AC: 582118 AN: 1457060 Hom.: 120991 Cov.: 31 AF XY: 0.397 AC XY: 287919 AN XY: 725090

Gnomad4 AFR exome AF: 0.701

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.348

Gnomad4 EAS exome AF: 0.140

Gnomad4 SAS exome AF: 0.404

Gnomad4 FIN exome AF: 0.448

Gnomad4 NFE exome AF: 0.393

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.472 AC: 71840 AN: 152052 Hom.: 18591 Cov.: 32 AF XY: 0.471 AC XY: 35016 AN XY: 74318

Gnomad4 AFR AF: 0.685

Gnomad4 AMR AF: 0.471

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.152

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.420

Alfa AF: 0.388 Hom.: 25468

Bravo AF: 0.484

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	7.9
Dann	Benign	0.74

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: rs1049817; hg19: chr2-27550967; COSMIC: COSV53129449; COSMIC: COSV53129449;