Genetic Variant GTF3A:c.202-947C>T (chr13-27426145-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002097.3(GTF3A):c.202-947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,260 control chromosomes in the GnomAD database, including 2,746 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 0.18 ( 2742 hom., cov: 32)

Exomes 𝑓: 0.24 ( 4 hom. )

Consequence

GTF3A
NM_002097.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.761

Publications

20 publications found

Variant links:

Genes affected

GTF3A (HGNC:4662): (general transcription factor IIIA) The product of this gene is a zinc finger protein with nine Cis[2]-His[2] zinc finger domains. It functions as an RNA polymerase III transcription factor to induce transcription of the 5S rRNA genes. The protein binds to a 50 bp internal promoter in the 5S genes called the internal control region (ICR), and nucleates formation of a stable preinitiation complex. This complex recruits the TFIIIC and TFIIIB transcription factors and RNA polymerase III to form the complete transcription complex. The protein is thought to be translated using a non-AUG translation initiation site in mammals based on sequence analysis, protein homology, and the size of the purified protein. [provided by RefSeq, Jul 2008]

GTF3A links:

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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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF3A	NM_002097.3 link	c.202-947C>T		intron_variant	Intron 1 of 8	ENST00000381140.10	NP_002088.2	Q92664-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF3A	ENST00000381140.10 link	c.202-947C>T		intron_variant	Intron 1 of 8	1	NM_002097.3	ENSP00000370532.5		Q92664-1A0A1X7SBT5

Frequencies

GnomAD3 genomes

AF:

0.185

AC:

28125

AN:

152046

Hom.:

2738

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.140

Gnomad AMR

AF:

0.131

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.140

Gnomad SAS

AF:

0.0966

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.188

Gnomad OTH

AF:

0.190

GnomAD4 exome

AF:

0.240

AC:

AN:

Hom.:

Cov.:

AF XY:

0.250

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.185

AC:

28137

AN:

152164

Hom.:

2742

Cov.:

AF XY:

0.185

AC XY:

13783

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.205

AC:

8500

AN:

41500

American (AMR)

AF:

0.130

AC:

1994

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.127

AC:

442

AN:

3472

East Asian (EAS)

AF:

0.141

AC:

728

AN:

5176

South Asian (SAS)

AF:

0.0961

AC:

464

AN:

4830

European-Finnish (FIN)

AF:

0.249

AC:

2630

AN:

10564

Middle Eastern (MID)

AF:

0.0986

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12818

AN:

68014

Other (OTH)

AF:

0.192

AC:

405

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1188

2375

3563

4750

5938

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

292

584

876

1168

1460

<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:

0.120

Hom.:

265

Bravo

AF:

0.178

Asia WGS

AF:

0.126

AC:

439

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.9

(source)

DANN

Benign

0.72

PhyloP100

-0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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