2-27335613-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001035521.3(GTF3C2):c.1561G>A(p.Ala521Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GTF3C2 NM_001035521.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.63

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]

GTF3C2-AS1 (HGNC:40269): (GTF3C2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17649719).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTF3C2	NM_001035521.3	c.1561G>A	p.Ala521Thr	missense_variant	10/19	ENST00000264720.8
GTF3C2-AS1	NR_038427.1	n.72C>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GTF3C2	ENST00000264720.8	c.1561G>A	p.Ala521Thr	missense_variant	10/19	1	NM_001035521.3	P1
GTF3C2-AS1	ENST00000590383.4	n.81C>T		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1396198 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 689270

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.1561G>A (p.A521T) alteration is located in exon 11 (coding exon 9) of the GTF3C2 gene. This alteration results from a G to A substitution at nucleotide position 1561, causing the alanine (A) at amino acid position 521 to be replaced by a threonine (T). 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	0.077
BayesDel_addAF	Benign	-0.063	T
BayesDel_noAF	Benign	-0.33
Cadd	Benign	22
Dann	Benign	0.97
DEOGEN2	Benign	0.13	T;T;T
Eigen	Benign	-0.028
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L;L;.
MutationTaster	Benign	0.95	D;D
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-0.29	N;N;.
REVEL	Benign	0.069
Sift	Benign	0.57	T;T;.
Sift4G	Uncertain	0.041	D;D;T
Polyphen		0.013	B;B;.
Vest4		0.21
MutPred		0.44		Gain of glycosylation at A521 (P = 0.0258);Gain of glycosylation at A521 (P = 0.0258);Gain of glycosylation at A521 (P = 0.0258);
MVP		0.46
MPC		1.6
ClinPred		0.74	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.084
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27558480;