rs8027679

Positions:

• chr15-59638573-G-C
• chr15-59638573-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004492.3(GTF2A2):​c.*559C>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 0.666 in 151,938 control chromosomes in the GnomAD database, including 33,956 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 0.67 (33928 hom., cov: 30)
  • Exomes 𝑓: 0.64 (28 hom.)
• Consequence: GTF2A2 NM_004492.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTF2A2	NM_004492.3	c.*559C>G		3_prime_UTR_variant	5/5	ENST00000396060.7	NP_004483.1
GTF2A2	NM_001320929.2	c.*559C>G		3_prime_UTR_variant	5/5		NP_001307858.1
GTF2A2	NM_001320930.2	c.*559C>G		3_prime_UTR_variant	6/6		NP_001307859.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTF2A2	ENST00000396060.7	c.*559C>G		3_prime_UTR_variant	5/5	1	NM_004492.3	ENSP00000379372	P1
GCNT3	ENST00000560210.1	n.352-1517G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.665 AC: 100943 AN: 151698 Hom.: 33884 Cov.: 30

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.706

Gnomad AMR AF: 0.627

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.662

GnomAD4 exome AF: 0.642 AC: 77 AN: 120 Hom.: 28 Cov.: 0 AF XY: 0.614 AC XY: 54 AN XY: 88

Gnomad4 AFR exome AF: 0.750

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.666 AC: 101049 AN: 151818 Hom.: 33928 Cov.: 30 AF XY: 0.660 AC XY: 48975 AN XY: 74154

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.628

Gnomad4 ASJ AF: 0.600

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.642

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.670

Gnomad4 OTH AF: 0.663

Alfa AF: 0.549 Hom.: 1525

Bravo AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.79

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

LitVar

Other links and lift over

dbSNP: rs8027679; hg19: chr15-59930772;