dbSNP rs8027679: GTF2A2:c.*559C>G (chr15-59638573-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.150

Variant links:

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]

GTF2A2 links:

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]

GCNT3 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=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
GTF2A2	NM_004492.3 link	c.*559C>G	3_prime_UTR_variant	Exon 5 of 5	ENST00000396060.7	NP_004483.1	P52657A0A024R5Z5B2R506
GTF2A2	NM_001320929.2 link	c.*559C>G	3_prime_UTR_variant	Exon 5 of 5		NP_001307858.1	P52657A0A024R5Z5
GTF2A2	NM_001320930.2 link	c.*559C>G	3_prime_UTR_variant	Exon 6 of 6		NP_001307859.1	P52657A0A024R5Z5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2A2	ENST00000396060 link	c.*559C>G		3_prime_UTR_variant	Exon 5 of 5	1	NM_004492.3	ENSP00000379372.2		P52657
GCNT3	ENST00000560210.1 link	n.352-1517G>C		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes

AF:

0.665

AC:

100943

AN:

151698

Hom.:

33884

Cov.:

show subpopulations

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:

AN:

120

Hom.:

Cov.:

AF XY:

0.614

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.750

AC:

AN:

Gnomad4 AMR exome

AF:

0.250

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AF:

0.667

AC:

AN:

Gnomad4 SAS exome

AF:

0.250

AC:

AN:

Gnomad4 FIN exome

AF:

0.500

AC:

AN:

Gnomad4 NFE exome

AF:

0.675

AC:

AN:

Gnomad4 Remaining exome

AF:

0.625

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

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:

0.666

AC:

101049

AN:

151818

Hom.:

33928

Cov.:

AF XY:

0.660

AC XY:

48975

AN XY:

74154

show subpopulations

Gnomad4 AFR

AF:

0.728

AC:

0.728363

AN:

0.728363

Gnomad4 AMR

AF:

0.628

AC:

0.627594

AN:

0.627594

Gnomad4 ASJ

AF:

0.600

AC:

0.600115

AN:

0.600115

Gnomad4 EAS

AF:

0.419

AC:

0.419323

AN:

0.419323

Gnomad4 SAS

AF:

0.642

AC:

0.642352

AN:

0.642352

Gnomad4 FIN

AF:

0.595

AC:

0.595061

AN:

0.595061

Gnomad4 NFE

AF:

0.670

AC:

0.669694

AN:

0.669694

Gnomad4 OTH

AF:

0.663

AC:

0.662879

AN:

0.662879

Heterozygous variant carriers

1711

3422

5134

6845

8556

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

804

1608

2412

3216

4020

<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:

0.549

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over