13-27426145-C-T

Variant names:

• chr13-27426145-C-T
• rs7988412
• NM_002097.3:c.202-947C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.761
• Publications: 20 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002097.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3A	NM_002097.3	MANE Select	c.202-947C>T		intron	N/A	NP_002088.2	Q92664-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF3A	ENST00000381140.10	TSL:1 MANE Select	c.202-947C>T		intron	N/A	ENSP00000370532.5	Q92664-1
	GTF3A	ENST00000419181.5	TSL:1	n.202-947C>T		intron	N/A	ENSP00000389655.1	H7BZH7
	GTF3A	ENST00000470606.5	TSL:2	n.735C>T		non_coding_transcript_exon	Exon 1 of 9

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28125 AN: 152046 Hom.: 2738 Cov.: 32

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: 23 AN: 96 Hom.: 4 Cov.: 0 AF XY: 0.250 AC XY: 17 AN XY: 68

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 11 AN: 44

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.205 AC: 9 AN: 44

Other (OTH) AF: 0.333 AC: 2 AN: 6

GnomAD4 genome AF: 0.185 AC: 28137 AN: 152164 Hom.: 2742 Cov.: 32 AF XY: 0.185 AC XY: 13783 AN XY: 74392

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: 29 AN: 294

European-Non Finnish (NFE) AF: 0.188 AC: 12818 AN: 68014

Other (OTH) AF: 0.192 AC: 405 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
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

Other links and lift over

dbSNP: rs7988412; hg19: chr13-28000282;