NM_004492.3:c.*559C>G

Variant names:

• chr15-59638573-G-C
• rs8027679
• NM_004492.3:c.*559C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004492.3. 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
	GTF2A2	NM_004492.3	MANE Select	c.*559C>G		3_prime_UTR	Exon 5 of 5	NP_004483.1	P52657
	GTF2A2	NM_001320929.2		c.*559C>G		3_prime_UTR	Exon 5 of 5	NP_001307858.1	P52657
	GTF2A2	NM_001320930.2		c.*559C>G		3_prime_UTR	Exon 6 of 6	NP_001307859.1	P52657

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTF2A2	ENST00000396060.7	TSL:1 MANE Select	c.*559C>G		3_prime_UTR	Exon 5 of 5	ENSP00000379372.2	P52657
	GTF2A2	ENST00000933396.1		c.*559C>G		3_prime_UTR	Exon 5 of 5	ENSP00000603455.1
	GCNT3	ENST00000560210.1	TSL:3	n.352-1517G>C		intron	N/A

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

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.667 AC: 12 AN: 18

South Asian (SAS) AF: 0.250 AC: 1 AN: 4

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.675 AC: 54 AN: 80

Other (OTH) AF: 0.625 AC: 5 AN: 8

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

African (AFR) AF: 0.728 AC: 30179 AN: 41434

American (AMR) AF: 0.628 AC: 9557 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2080 AN: 3466

East Asian (EAS) AF: 0.419 AC: 2157 AN: 5144

South Asian (SAS) AF: 0.642 AC: 3091 AN: 4812

European-Finnish (FIN) AF: 0.595 AC: 6241 AN: 10488

Middle Eastern (MID) AF: 0.712 AC: 208 AN: 292

European-Non Finnish (NFE) AF: 0.670 AC: 45495 AN: 67934

Other (OTH) AF: 0.663 AC: 1400 AN: 2112

Alfa AF: 0.549 Hom.: 1525

Bravo AF: 0.665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.2
DANN	Benign	0.79
PhyloP100		-0.15
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: rs8027679; hg19: chr15-59930772;