Genetic Variant GTF3C2:p.Pro782Pro (chr2-27328100-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.246

Publications

44 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C2	NM_001035521.3 link	c.2346T>C	p.Pro782Pro	synonymous_variant	Exon 17 of 19	ENST00000264720.8	NP_001030598.1	Q8WUA4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GTF3C2	ENST00000264720.8 link	c.2346T>C	p.Pro782Pro	synonymous_variant	Exon 17 of 19	1	NM_001035521.3	ENSP00000264720.3	Q8WUA4-1
GTF3C2	ENST00000415683.2 link	n.*68T>C		non_coding_transcript_exon_variant	Exon 5 of 6	5		ENSP00000414422.2	H7C3X9
GTF3C2	ENST00000415683.2 link	n.*68T>C		3_prime_UTR_variant	Exon 5 of 6	5		ENSP00000414422.2	H7C3X9

Frequencies

GnomAD3 genomes

AF:

0.472

AC:

71710

AN:

151934

Hom.:

18532

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.397

AC XY:

287919

AN XY:

725090

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

16327

32654

48981

65308

81635

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.472

AC:

71840

AN:

152052

Hom.:

18591

Cov.:

AF XY:

0.471

AC XY:

35016

AN XY:

74318

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1812

3623

5435

7246

9058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

7.9

(source)

DANN

Benign

0.74

PhyloP100

-0.25

PromoterAI

0.0030

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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2-27328100-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over