rs8027421

Variant names:

• chr15-59638666-A-T
• rs8027421
• NM_004492.3:c.*466T>A

Variant summary

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

The NM_004492.3(GTF2A2):​c.*466T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0635 in 152,496 control chromosomes in the GnomAD database, including 596 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 0.064 (594 hom., cov: 32)
  • Exomes 𝑓: 0.042 (2 hom.)
• Consequence: GTF2A2 NM_004492.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0270
• Publications: 4 publications found

Genes affected

GTF2A2 (HGNC:4647): (general transcription factor IIA subunit 2) Accurate transcription initiation on TATA-containing class II genes involves the ordered assembly of RNA polymerase II (POLR2A; MIM 180660) and the general initiation factors TFIIA, TFIIB (MIM 189963), TFIID (MIM 313650), TFIIE (MIM 189962), TFIIF (MIM 189968), TFIIG/TFIIJ, and TFIIH (MIM 189972). The first step involves recognition of the TATA element by the TATA-binding subunit (TBP; MIM 600075) and may be regulated by TFIIA, a factor that interacts with both TBP and a TBP-associated factor (TAF; MIM 600475) in TFIID. TFIIA has 2 subunits (43 and 12 kD) in yeast and 3 subunits in higher eukaryotes. In HeLa extracts, it consists of a 35-kD alpha subunit and a 19-kD beta subunit encoded by the N- and C-terminal regions of GTF2A1 (MIM 600520), respectively, and a 12-kD gamma subunit encoded by GTF2A2 (DeJong et al., 1995 [PubMed 7724559]).[supplied by OMIM, Mar 2008]

GCNT3 (HGNC:4205): (glucosaminyl (N-acetyl) transferase 3, mucin type) This gene encodes a member of the N-acetylglucosaminyltransferase family. The encoded protein is a beta-6-N-acetylglucosamine-transferase that catalyzes the formation of core 2 and core 4 O-glycans on mucin-type glycoproteins.[provided by RefSeq, Apr 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2A2	NM_004492.3	c.*466T>A		3_prime_UTR_variant	Exon 5 of 5	ENST00000396060.7	NP_004483.1
GTF2A2	NM_001320929.2	c.*466T>A		3_prime_UTR_variant	Exon 5 of 5		NP_001307858.1
GTF2A2	NM_001320930.2	c.*466T>A		3_prime_UTR_variant	Exon 6 of 6		NP_001307859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2A2	ENST00000396060.7	c.*466T>A		3_prime_UTR_variant	Exon 5 of 5	1	NM_004492.3	ENSP00000379372.2

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9660 AN: 152114 Hom.: 593 Cov.: 32

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.0530

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0240

Gnomad OTH AF: 0.0450

GnomAD4 exome AF: 0.0417 AC: 11 AN: 264 Hom.: 2 Cov.: 0 AF XY: 0.0506 AC XY: 8 AN XY: 158

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 8

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6

East Asian (EAS) AF: 0.400 AC: 8 AN: 20

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0143 AC: 3 AN: 210

Other (OTH) AF: 0.00 AC: 0 AN: 10

GnomAD4 genome AF: 0.0635 AC: 9674 AN: 152232 Hom.: 594 Cov.: 32 AF XY: 0.0684 AC XY: 5093 AN XY: 74444

African (AFR) AF: 0.109 AC: 4534 AN: 41534

American (AMR) AF: 0.0285 AC: 436 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00634 AC: 22 AN: 3470

East Asian (EAS) AF: 0.251 AC: 1299 AN: 5172

South Asian (SAS) AF: 0.219 AC: 1057 AN: 4822

European-Finnish (FIN) AF: 0.0530 AC: 562 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0240 AC: 1632 AN: 68016

Other (OTH) AF: 0.0474 AC: 100 AN: 2110

Alfa AF: 0.0393 Hom.: 21

Bravo AF: 0.0590

Asia WGS AF: 0.199 AC: 690 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.29
DANN	Benign	0.70
PhyloP100		-0.027
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: rs8027421; hg19: chr15-59930865;