NM_001035521.3:c.2522G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001035521.3(GTF3C2):​c.2522G>A​(p.Arg841His) variant causes a missense change. The variant allele was found at a frequency of 0.0000237 in 1,603,776 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GTF3C2
NM_001035521.3 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.90
Variant links:
Genes affected
GTF3C2 (HGNC:4665): (general transcription factor IIIC subunit 2) Contributes to DNA binding activity. Involved in transcription by RNA polymerase III. Located in nucleoplasm. Part of transcription factor TFIIIC complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTF3C2NM_001035521.3 linkc.2522G>A p.Arg841His missense_variant Exon 19 of 19 ENST00000264720.8 NP_001030598.1 Q8WUA4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTF3C2ENST00000264720.8 linkc.2522G>A p.Arg841His missense_variant Exon 19 of 19 1 NM_001035521.3 ENSP00000264720.3 Q8WUA4-1

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151786
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000255
AC:
37
AN:
1451990
Hom.:
0
Cov.:
28
AF XY:
0.0000277
AC XY:
20
AN XY:
723060
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000335
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151786
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74104
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000756
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2522G>A (p.R841H) alteration is located in exon 20 (coding exon 18) of the GTF3C2 gene. This alteration results from a G to A substitution at nucleotide position 2522, causing the arginine (R) at amino acid position 841 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Pathogenic
30
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.42
T;T
Eigen
Uncertain
0.32
Eigen_PC
Uncertain
0.44
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.88
.;D
M_CAP
Benign
0.033
D
MetaRNN
Uncertain
0.67
D;D
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
1.6
L;L
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-2.2
N;N
REVEL
Uncertain
0.34
Sift
Benign
0.030
D;D
Sift4G
Benign
0.072
T;T
Polyphen
1.0
D;D
Vest4
0.69
MutPred
0.48
Loss of methylation at R841 (P = 0.0355);Loss of methylation at R841 (P = 0.0355);
MVP
0.38
MPC
0.66
ClinPred
0.92
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.25
gMVP
0.76

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.

Other links and lift over

dbSNP: rs1322952115; hg19: chr2-27549756; API