2-27328038-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001035521.3(GTF3C2):ā€‹c.2408T>Cā€‹(p.Leu803Ser) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000686 in 1,457,184 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

GTF3C2
NM_001035521.3 missense, splice_region

Scores

2
9
8
Splicing: ADA: 0.2600
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GTF3C2NM_001035521.3 linkc.2408T>C p.Leu803Ser missense_variant, splice_region_variant 17/19 ENST00000264720.8 NP_001030598.1 Q8WUA4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GTF3C2ENST00000264720.8 linkc.2408T>C p.Leu803Ser missense_variant, splice_region_variant 17/191 NM_001035521.3 ENSP00000264720.3 Q8WUA4-1
GTF3C2ENST00000415683.2 linkn.*130T>C splice_region_variant, non_coding_transcript_exon_variant 5/65 ENSP00000414422.2 H7C3X9
GTF3C2ENST00000415683.2 linkn.*130T>C 3_prime_UTR_variant 5/65 ENSP00000414422.2 H7C3X9

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD3 exomes
AF:
0.00000405
AC:
1
AN:
246994
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
133694
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000888
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457184
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725016
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
30
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 09, 2024The c.2408T>C (p.L803S) alteration is located in exon 18 (coding exon 16) of the GTF3C2 gene. This alteration results from a T to C substitution at nucleotide position 2408, causing the leucine (L) at amino acid position 803 to be replaced by a serine (S). 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
Pathogenic
0.66
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.050
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T;T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.58
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.73
.;T
M_CAP
Benign
0.023
T
MetaRNN
Uncertain
0.63
D;D
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.4
L;L
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.1
N;N
REVEL
Uncertain
0.40
Sift
Benign
0.067
T;T
Sift4G
Uncertain
0.0020
D;D
Polyphen
1.0
D;D
Vest4
0.60
MutPred
0.46
Gain of disorder (P = 0.011);Gain of disorder (P = 0.011);
MVP
0.39
MPC
0.80
ClinPred
0.87
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.062
gMVP
0.72

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.26
dbscSNV1_RF
Benign
0.58
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: rs781182085; hg19: chr2-27550905; API