Genetic Variant GTF3C4:c.*614A>G (chr9-132689559-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_012204.4(GTF3C4):c.*614A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 152,440 control chromosomes in the GnomAD database, including 18,083 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 0.48 ( 18043 hom., cov: 32)

Exomes 𝑓: 0.36 ( 40 hom. )

Consequence

GTF3C4
NM_012204.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.764

Publications

9 publications found

Variant links:

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]

GTF3C4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3C4	NM_012204.4 link	c.*614A>G		3_prime_UTR_variant	Exon 5 of 5	ENST00000372146.5	NP_036336.2	Q9UKN8B3KNH2
GTF3C4	NR_133925.1 link	n.3685A>G		non_coding_transcript_exon_variant	Exon 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3C4	ENST00000372146.5 link	c.*614A>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_012204.4	ENSP00000361219.4		Q9UKN8

Frequencies

GnomAD3 genomes

AF:

0.477

AC:

72424

AN:

151876

Hom.:

18014

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.492

Gnomad ASJ

AF:

0.352

Gnomad EAS

AF:

0.565

Gnomad SAS

AF:

0.406

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.392

Gnomad OTH

AF:

0.439

GnomAD4 exome

AF:

0.363

AC:

162

AN:

446

Hom.:

Cov.:

AF XY:

0.395

AC XY:

AN XY:

238

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.554

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.667

AC:

AN:

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.316

AC:

110

AN:

348

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.477

AC:

72506

AN:

151994

Hom.:

18043

Cov.:

AF XY:

0.480

AC XY:

35678

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.613

AC:

25396

AN:

41432

American (AMR)

AF:

0.492

AC:

7533

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.352

AC:

1220

AN:

3468

East Asian (EAS)

AF:

0.565

AC:

2921

AN:

5170

South Asian (SAS)

AF:

0.404

AC:

1947

AN:

4816

European-Finnish (FIN)

AF:

0.515

AC:

5432

AN:

10554

Middle Eastern (MID)

AF:

0.337

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.392

AC:

26664

AN:

67940

Other (OTH)

AF:

0.437

AC:

923

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1863

3727

5590

7454

9317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

648

1296

1944

2592

3240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.439

Hom.:

7164

Bravo

AF:

0.486

Asia WGS

AF:

0.480

AC:

1667

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.6

(source)

DANN

Benign

0.85

PhyloP100

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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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