2-27328100-A-G

Variant names:

• chr2-27328100-A-G
• rs1049817
• NM_001035521.3:c.2346T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_001035521.3(GTF3C2):​c.2346T>C​(p.Pro782Pro) 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
• Publications: 44 publications found

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.018).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001035521.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C2	NM_001035521.3	MANE Select	c.2346T>C	p.Pro782Pro	synonymous	Exon 17 of 19	NP_001030598.1
	GTF3C2	NM_001318909.4		c.2346T>C	p.Pro782Pro	synonymous	Exon 17 of 19	NP_001305838.2
	GTF3C2	NM_001388380.3		c.2346T>C	p.Pro782Pro	synonymous	Exon 18 of 20	NP_001375309.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3C2	ENST00000264720.8	TSL:1 MANE Select	c.2346T>C	p.Pro782Pro	synonymous	Exon 17 of 19	ENSP00000264720.3
	GTF3C2	ENST00000359541.6	TSL:1	c.2346T>C	p.Pro782Pro	synonymous	Exon 17 of 19	ENSP00000352536.2
	GTF3C2	ENST00000454704.5	TSL:1	c.870T>C	p.Pro290Pro	synonymous	Exon 8 of 10	ENSP00000393429.1

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

GnomAD2 exomes AF: 0.419 AC: 104001 AN: 248488 AF XY: 0.407

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 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

African (AFR) AF: 0.701 AC: 23234 AN: 33136

American (AMR) AF: 0.551 AC: 24047 AN: 43658

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9064 AN: 26052

East Asian (EAS) AF: 0.140 AC: 5558 AN: 39632

South Asian (SAS) AF: 0.404 AC: 34617 AN: 85690

European-Finnish (FIN) AF: 0.448 AC: 23892 AN: 53386

Middle Eastern (MID) AF: 0.356 AC: 2045 AN: 5744

European-Non Finnish (NFE) AF: 0.393 AC: 435799 AN: 1109566

Other (OTH) AF: 0.396 AC: 23862 AN: 60196

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

African (AFR) AF: 0.685 AC: 28432 AN: 41494

American (AMR) AF: 0.471 AC: 7191 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3466

East Asian (EAS) AF: 0.152 AC: 785 AN: 5172

South Asian (SAS) AF: 0.406 AC: 1954 AN: 4818

European-Finnish (FIN) AF: 0.447 AC: 4720 AN: 10556

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26304 AN: 67966

Other (OTH) AF: 0.420 AC: 887 AN: 2114

Alfa AF: 0.408 Hom.: 57446

Bravo AF: 0.484

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.9
DANN	Benign	0.74
PhyloP100		-0.25
PromoterAI		0.0030	Neutral
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: rs1049817; hg19: chr2-27550967; COSMIC: COSV53129449; COSMIC: COSV53129449;